rs781670345
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000260.4(MYO7A):c.3797A>G(p.Asp1266Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,599,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.3797A>G | p.Asp1266Gly | missense_variant | 30/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.3797A>G | p.Asp1266Gly | missense_variant | 30/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000264 AC: 4AN: 151746Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000884 AC: 2AN: 226220Hom.: 0 AF XY: 0.00000818 AC XY: 1AN XY: 122290
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1447920Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2AN XY: 718564
GnomAD4 genome ? AF: 0.0000264 AC: 4AN: 151746Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74086
ClinVar
Submissions by phenotype
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Apr 09, 2018 | - - |
Usher syndrome type 1B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 05, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2021 | This sequence change replaces aspartic acid with glycine at codon 1266 of the MYO7A protein (p.Asp1266Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This missense change has been observed in individual(s) with non-syndromic hearing loss (PMID: 26969326). ClinVar contains an entry for this variant (Variation ID: 557841). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at