17-18143580-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016239.4(MYO15A):c.5925G>T(p.Trp1975Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MYO15A
NM_016239.4 missense
NM_016239.4 missense
Scores
2
13
Clinical Significance
Conservation
PhyloP100: 3.20
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.5925G>T | p.Trp1975Cys | missense_variant | 26/66 | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.5925G>T | p.Trp1975Cys | missense_variant | 26/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1408686Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 695768
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1408686
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
695768
Gnomad4 AFR exome
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Gnomad4 SAS exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
5
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 | Dec 13, 2016 | The p.Trp1975Cys variant in MYO15A has not been previously reported in individua ls with hearing loss or in large population studies. Computational prediction to ols and conservation analysis suggest that the p.Trp1975Cys variant may not impa ct the protein, though this information is not predictive enough to rule out pat hogenicity. In summary, the clinical significance of the p.Trp1975Cys variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
Sift4G
Uncertain
D;D;.
Polyphen
0.68
.;P;P
Vest4
MutPred
Loss of MoRF binding (P = 0.0266);Loss of MoRF binding (P = 0.0266);Loss of MoRF binding (P = 0.0266);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -14
DS_DG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at