rs1199012623
Variant summary
Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PVS1PM2PP3_ModeratePP5_Very_Strong
The NM_000260.4(MYO7A):βc.4838delβ(p.Asp1613ValfsTer32) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 1,595,968 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. D1613D) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000260.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.4838del | p.Asp1613ValfsTer32 | frameshift_variant | 35/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.4838del | p.Asp1613ValfsTer32 | frameshift_variant | 35/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000828 AC: 2AN: 241422Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 130852
GnomAD4 exome AF: 0.00000416 AC: 6AN: 1443626Hom.: 1 Cov.: 33 AF XY: 0.00000420 AC XY: 3AN XY: 714606
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74504
ClinVar
Submissions by phenotype
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 03, 2018 | - - |
Usher syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | This sequence change creates a premature translational stop signal (p.Asp1613Valfs*32) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 438178). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 18181211). This variant is present in population databases (no rsID available, gnomAD 0.007%). - |
Hearing loss, autosomal recessive Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at