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Intellectual disability

Gene: FAM160B1

Red List (low evidence)

FAM160B1 (family with sequence similarity 160 member B1)
EnsemblGeneIds (GRCh38): ENSG00000151553
EnsemblGeneIds (GRCh37): ENSG00000151553
OMIM: 617312, Gene2Phenotype
FAM160B1 is in 1 panel

2 reviews

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Gene added by external reviewer, and promoted from grey to Red as the function of the protein/gene is still unknown at this stage. One family and another unrelated individual reported with developmental delay/ID and variants in this gene, however this will be kept red until further evidence arises.
Created: 27 Nov 2019, 5:12 p.m. | Last Modified: 27 Nov 2019, 5:12 p.m.
Panel Version: 2.1127

Konstantinos Varvagiannis (Other)

I don't know

Anazi et al. (2017 - PMID: 27431290) in a study of 337 subjects with ID, reported on a consanguineous family (15DG2696) with 3 affected sibs. The proband, a 7 y.o. boy had hypotonia, DD, mild ID (IQ of 69), some facial dysmorphic features as well as increased skin elasticity and joint hypermobility. Initial investigations included metabolic testing for OA and CDGs, FMR1 and aCGH. A 4 y.o. sister and a 3 y.o. brother of the proband had similar presentation of DD. Exome sequencing, autozygosity mapping and segregation studies suggested a FAM160B1 hmz missense SNV as the likely causal variant (NM_001135051.1:c.248T>C or p.Leu83Pro). There were no other candidate variants. As the encoded protein has a yet unknown function, with uncertain in silico 3D modeling, the authors speculated disruption of helices affecting fold/(ligand binding) function as the underlying effect of this variant.

Mavioğlu et al. (2019 - PMID: 31353455) reported on a 38 y.o. female with history of motor and language delay, severe ID, ataxia, behavioral abrnormalities as well as some dysmorphic features. This individual was born to consanguineous parents (2nd cousins). There was history of a deceased, similarly affected sib. Initial investigations included metabolic work-up (plasma AA, urinary OA) and karyotyping. SNP genotyping in the family (parents, affected sib, 3 unaffected sibs) and multipoint linkage analysis for AR inheritance, yielded a maximum LOD score of 2.15. Selection of homozygous regions unique to the patient (but not present in unaffected sibs) did not suggest any known ID gene. Exome sequencing of the proband, with analysis of the variants in candidate regions revealed a homozygous stopgain SNV (NM_020940.4:c.115G>T or p.Glu39*) as the best candidate variant (with few others not considered to be relevant). FAM160B1 has a pLI of 1, LoF variants in public databases have MAFs below 0.000034 with no recorded homozygotes. In silico predictions suggested a deleterious effect (CADD score of 40, etc). The previous report by Anazi and fulfilment of the ACMG criteria for its classification of this variant as pathogenic led to its consideration as causal of the patient's phenotype.

Study of the expression of the 2 isoforms of the gene (isoform1: NM_020940, 2:NM_001135051) revealed that the first is ubiquitously expressed and the second only in testes. [To my understanding the 2 isoforms seem to differ only in their last exon, the 2 reported variants affecting both isoforms - http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr10%3A116577123%2D116663023&hgsid=777553295_dPP9DgaheaF82gTRTfZO6XS5lEzA ]

The function of this gene remains unknown. Animal models/phenotypes are probably not available.

There is no associated phenotype in OMIM/G2P. SysID lists FAM160B1 as a candidate ID gene.
FAM160B1 is not commonly included in gene panels for ID offered by diagnostic laboratories.

As a result this gene can be considered for inclusion in the current panel probably with amber (2 families/variants, variable ID as a feature) or red rating pending further evidence (given the partial phenotypic overlap, unknown function of the gene, variants not further studied, no animal models).
Sources: Literature
Created: 11 Nov 2019, 5:07 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of the face

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
Phenotypes
  • Central hypotonia
  • Global developmental delay
  • Intellectual disability
  • Abnormality of the face
OMIM
617312
Clinvar variants
Variants in FAM160B1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

27 Nov 2019, Gel status: 1

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: fam160b1 has been classified as Red List (Low Evidence).

11 Nov 2019, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: FAM160B1 was added gene: FAM160B1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: FAM160B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM160B1 were set to 27431290; 31353455 Phenotypes for gene: FAM160B1 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of the face Penetrance for gene: FAM160B1 were set to Complete Review for gene: FAM160B1 was set to AMBER