11-77197517-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000260.4(MYO7A):c.4360G>A(p.Val1454Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000051 in 1,607,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. V1454V) 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_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.4360G>A | p.Val1454Ile | missense_variant | 33/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.4360G>A | p.Val1454Ile | missense_variant | 33/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000252 AC: 6AN: 238054Hom.: 0 AF XY: 0.0000155 AC XY: 2AN XY: 128886
GnomAD4 exome AF: 0.0000543 AC: 79AN: 1455102Hom.: 0 Cov.: 31 AF XY: 0.0000526 AC XY: 38AN XY: 722930
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74508
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 | Mar 17, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1454 of the MYO7A protein (p.Val1454Ile). This variant is present in population databases (rs397516309, gnomAD 0.04%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 26338283). ClinVar contains an entry for this variant (Variation ID: 43237). 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 not 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 17, 2011 | Val1454Ile in exon 33 of MYO7A: This variant is not expected to have clinical si gnificance because computational analyses (PolyPhen2, SIFT, AlignGVGD) do not su ggest a high likelihood of impact to the protein. Of note, fruitfly has an isole ucine at this position despite high nearby amino acid conservation. - |
Autosomal recessive nonsyndromic hearing loss 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at