17-18142800-C-G

Position:

• chr17-18142800-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016239.4(MYO15A):​c.5870C>G​(p.Ser1957Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO15A NM_016239.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.97

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3708409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO15A	NM_016239.4	c.5870C>G	p.Ser1957Cys	missense_variant	25/66	ENST00000647165.2	NP_057323.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2	c.5870C>G	p.Ser1957Cys	missense_variant	25/66		NM_016239.4	ENSP00000495481.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;D;D
Eigen	Benign	0.058
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	T;.;T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Uncertain	-0.094	T
MutationAssessor	Uncertain	2.3	.;M;M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	.;D;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.0040	.;D;.
Sift4G	Pathogenic	0.0010	D;D;.
Polyphen		0.060	.;B;B
Vest4		0.53
MutPred		0.46		Gain of catalytic residue at L1958 (P = 0.0179);Gain of catalytic residue at L1958 (P = 0.0179);Gain of catalytic residue at L1958 (P = 0.0179);
MVP		0.79
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.22
gMVP		0.43

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

Other links and lift over

dbSNP: rs876657901; hg19: chr17-18046114;