rs1555090442
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000260.4(MYO7A):c.3610C>A(p.Pro1204Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,754 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P1204P) 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 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.3610C>A | p.Pro1204Thr | missense_variant | 28/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.3610C>A | p.Pro1204Thr | missense_variant | 28/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249128Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135186
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461592Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727072
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74314
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1204 of the MYO7A protein (p.Pro1204Thr). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with autosomal recessive Usher syndrome (PMID: 24498627, 33576163, 33576794). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 556065). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. - |
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 10, 2018 | - - |
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 | Apr 18, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at