rs766482387
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016239.4(MYO15A):āc.869A>Gā(p.Tyr290Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,064 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 Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
MYO15A
NM_016239.4 missense
NM_016239.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 1.21
Genes affected
MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.122905284).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.869A>G | p.Tyr290Cys | missense_variant | 2/66 | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.869A>G | p.Tyr290Cys | missense_variant | 2/66 | NM_016239.4 | P1 | ||
MYO15A | ENST00000583079.1 | n.502A>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000124 AC: 3AN: 241952Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132458
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GnomAD4 exome AF: 0.00000344 AC: 5AN: 1454064Hom.: 0 Cov.: 36 AF XY: 0.00000276 AC XY: 2AN XY: 723716
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ExAC
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 07, 2016 | The p.Tyr290Cys variant in MYO15A has not been previously reported in individual s with hearing loss. This variant has been identified in 1/16442 South Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs766482387). Although this variant has been seen in the general popul ation, its frequency is not high enough to rule out a pathogenic role. Computati onal prediction tools and conservation analyses do not provide strong support fo r or against an impact to the protein. In summary, the clinical significance of the p.Tyr290Cys variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;L;L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
.;D;.
REVEL
Uncertain
Sift
Uncertain
.;D;.
Sift4G
Pathogenic
D;D;.
Polyphen
0.037
.;B;B
Vest4
MutPred
Loss of phosphorylation at Y290 (P = 0.0259);Loss of phosphorylation at Y290 (P = 0.0259);Loss of phosphorylation at Y290 (P = 0.0259);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
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