rs781951909
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000260.4(MYO7A):c.1591C>T(p.Gln531Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000205 in 1,461,664 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MYO7A
NM_000260.4 stop_gained
NM_000260.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 5.66
Genes affected
MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-77162889-C-T is Pathogenic according to our data. Variant chr11-77162889-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 553105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77162889-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.1591C>T | p.Gln531Ter | stop_gained | 14/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.1591C>T | p.Gln531Ter | stop_gained | 14/49 | 1 | NM_000260.4 | ||
MYO7A | ENST00000458637.6 | c.1591C>T | p.Gln531Ter | stop_gained | 14/49 | 1 | P1 | ||
MYO7A | ENST00000409619.6 | c.1558C>T | p.Gln520Ter | stop_gained | 15/50 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249266Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135220
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461664Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727122
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jul 27, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2023 | This sequence change creates a premature translational stop signal (p.Gln531*) 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). This variant is present in population databases (rs781951909, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 18181211). ClinVar contains an entry for this variant (Variation ID: 553105). For these reasons, this variant has been classified as Pathogenic. - |
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at