Variant 17-18150908-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016239.4(MYO15A):c.7468G>T(p.Ala2490Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,448,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2490T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MYO15A
NM_016239.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.471

Variant links:

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]

MYO15A links:

LOC124903944 (HGNC:):

LOC124903944 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031119853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO15A	NM_016239.4 linkuse as main transcript	c.7468G>T	p.Ala2490Ser	missense_variant	38/66	ENST00000647165.2	NP_057323.3	Q9UKN7-1
MYO15A	XM_017024715.3 linkuse as main transcript	c.7471G>T	p.Ala2491Ser	missense_variant	36/64		XP_016880204.1
MYO15A	XM_017024714.3 linkuse as main transcript	c.7408G>T	p.Ala2470Ser	missense_variant	35/63		XP_016880203.1
LOC124903944	XR_007065652.1 linkuse as main transcript	n.377+695C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2 linkuse as main transcript	c.7468G>T	p.Ala2490Ser	missense_variant	38/66		NM_016239.4	ENSP00000495481.1		Q9UKN7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000445

AC:

AN:

224928

Hom.:

AF XY:

0.00

AC XY:

AN XY:

122076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000998

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1448860

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719744

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000163

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000385

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.1

DANN

Benign

0.78

DEOGEN2

Benign

0.0072

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.47

T;.;T

M_CAP

Benign

0.059

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

-0.69

.;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.51

.;N;.

REVEL

Benign

0.21

Sift

Benign

0.15

.;T;.

Sift4G

Benign

0.55

T;T;.

Polyphen

0.0010

.;B;B

Vest4

0.061

MutPred

0.098

Gain of glycosylation at A2490 (P = 0.0056);Gain of glycosylation at A2490 (P = 0.0056);Gain of glycosylation at A2490 (P = 0.0056);

MVP

0.29

ClinPred

0.021

GERP RS

-0.71

Varity_R

0.044

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over