chr11-77189367-G-A
Variant summary
Our verdict is Uncertain significance. Variant got -1 ACMG points: 0P and 1B. BP2
This summary comes from the ClinGen Evidence Repository: The c.3527G>A (p.Ser1176Asn) variant in MYO7A was present in 0.057% (lower bound of the 95% CI of 33/42036) of African alleles in gnomAD v3 (BS1_Supporting not met). It has been observed in at least 3 individuals with Usher syndrome type 1. However, in one proband the p.Ser1176Asn variant was observed in cis with another pathogenic/likely pathogenic variant in MYO7A (BP2; PMID:26969326). The remaining probands did not have other pathogenic or likely pathogenic variants in MYO7A identified (PM3 and PP4 not met; PMID:27344577, 27460420, 31479088). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BP2. LINK:https://erepo.genome.network/evrepo/ui/classification/CA242907/MONDO:0019501/005
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.3527G>A | p.Ser1176Asn | missense_variant | 28/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.3527G>A | p.Ser1176Asn | missense_variant | 28/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000763 AC: 19AN: 248872Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135116
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461338Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 726944
GnomAD4 genome AF: 0.000236 AC: 36AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.000295 AC XY: 22AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 29, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 14, 2020 | This variant is associated with the following publications: (PMID: 26969326, 31479088, 27460420, 27344577, 33297549) - |
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 20, 2017 | - - |
Usher syndrome Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Hearing Loss Variant Curation Expert Panel | May 20, 2020 | The c.3527G>A (p.Ser1176Asn) variant in MYO7A was present in 0.057% (lower bound of the 95% CI of 33/42036) of African alleles in gnomAD v3 (BS1_Supporting not met). It has been observed in at least 3 individuals with Usher syndrome type 1. However, in one proband the p.Ser1176Asn variant was observed in cis with another pathogenic/likely pathogenic variant in MYO7A (BP2; PMID: 26969326). The remaining probands did not have other pathogenic or likely pathogenic variants in MYO7A identified (PM3 and PP4 not met; PMID: 27344577, 27460420, 31479088). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BP2. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | Apr 21, 2023 | - - |
Usher syndrome type 1;C1832475:Autosomal dominant nonsyndromic hearing loss 11;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 18, 2022 | - - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jun 19, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at