rs781922871
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate
The NM_000260.4(MYO7A):āc.904C>Gā(p.Arg302Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,124 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R302H) has been classified as Likely benign.
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.904C>G | p.Arg302Gly | missense_variant | 9/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.904C>G | p.Arg302Gly | missense_variant | 9/49 | 1 | NM_000260.4 | ||
MYO7A | ENST00000458637.6 | c.904C>G | p.Arg302Gly | missense_variant | 9/49 | 1 | P1 | ||
MYO7A | ENST00000409619.6 | c.871C>G | p.Arg291Gly | missense_variant | 10/50 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248104Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134704
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460904Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726714
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 13, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 302 of the MYO7A protein (p.Arg302Gly). This variant is present in population databases (rs781922871, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function. 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