chr11-77162179-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000260.4(MYO7A):āc.1403A>Gā(p.His468Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,601,664 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. H468H) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.1403A>G | p.His468Arg | missense_variant | 13/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.1403A>G | p.His468Arg | missense_variant | 13/49 | 1 | NM_000260.4 | ||
MYO7A | ENST00000458637.6 | c.1403A>G | p.His468Arg | missense_variant | 13/49 | 1 | P1 | ||
MYO7A | ENST00000409619.6 | c.1370A>G | p.His457Arg | missense_variant | 14/50 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000144 AC: 33AN: 229936Hom.: 1 AF XY: 0.000113 AC XY: 14AN XY: 123820
GnomAD4 exome AF: 0.000186 AC: 269AN: 1449500Hom.: 1 Cov.: 31 AF XY: 0.000161 AC XY: 116AN XY: 719336
GnomAD4 genome AF: 0.000118 AC: 18AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 30, 2022 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 468 of the MYO7A protein (p.His468Arg). This variant is present in population databases (rs200304238, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with non-syndromic hearing loss (PMID: 27068579). ClinVar contains an entry for this variant (Variation ID: 553342). 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2022 | Identified with a second MYO7A variant in a patient with prelingual nonsyndromic hearing loss in published literature (Sommen et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27068579) - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Aug 16, 2017 | - - |
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 | Aug 05, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at