rs199953758
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016239.4(MYO15A):c.7367C>A(p.Ala2456Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,092 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
MYO15A
NM_016239.4 missense
NM_016239.4 missense
Scores
6
9
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.19
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]
Genome browser will be placed here
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.7367C>A | p.Ala2456Asp | missense_variant | 37/66 | ENST00000647165.2 | NP_057323.3 | |
MYO15A | XM_017024715.3 | c.7370C>A | p.Ala2457Asp | missense_variant | 35/64 | XP_016880204.1 | ||
MYO15A | XM_017024714.3 | c.7307C>A | p.Ala2436Asp | missense_variant | 34/63 | XP_016880203.1 | ||
LOC124903944 | XR_007065652.1 | n.377+866G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.7367C>A | p.Ala2456Asp | missense_variant | 37/66 | NM_016239.4 | ENSP00000495481.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000481 AC: 1AN: 207972Hom.: 0 AF XY: 0.00000890 AC XY: 1AN XY: 112322
GnomAD3 exomes
AF:
AC:
1
AN:
207972
Hom.:
AF XY:
AC XY:
1
AN XY:
112322
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.96e-7 AC: 1AN: 1436092Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 712086
GnomAD4 exome
AF:
AC:
1
AN:
1436092
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
712086
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;.
REVEL
Pathogenic
Sift
Uncertain
.;D;.
Sift4G
Pathogenic
D;D;.
Polyphen
1.0
.;D;D
Vest4
MutPred
Gain of ubiquitination at K2460 (P = 0.1025);Gain of ubiquitination at K2460 (P = 0.1025);Gain of ubiquitination at K2460 (P = 0.1025);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at