rs373886432
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000260.4(MYO7A):c.5641G>A(p.Gly1881Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,610,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G1881G) has been classified as Likely benign.
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.5641G>A | p.Gly1881Arg | missense_variant | 41/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.5641G>A | p.Gly1881Arg | missense_variant | 41/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151984Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000164 AC: 4AN: 243352Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 132098
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1458648Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 725314
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 23, 2016 | The p.Gly1881Arg variant in MYO7A has not been previously reported in individual s with hearing loss or Usher syndrome. This variant has been identified in 1/457 54 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs373886432); however, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis suggest that the p.Gly1881Arg variant may impact the protein, though th is information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Gly1881Arg variant is uncertain. - |
Usher syndrome type 1B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 17, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces glycine with arginine at codon 1881 of the MYO7A protein (p.Gly1881Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs373886432, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 504649). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
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 15, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at