chr17-18161424-G-T

Variant names:

• chr17-18161424-G-T
• NM_016239.4:c.9494G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016239.4(MYO15A):​c.9494G>T​(p.Arg3165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYO15A NM_016239.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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]

ACMG classification

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 rank	MANE	Protein	UniProt
MYO15A	NM_016239.4	c.9494G>T	p.Arg3165Leu	missense_variant	Exon 57 of 66	ENST00000647165.2	NP_057323.3
MYO15A	XM_017024715.3	c.9497G>T	p.Arg3166Leu	missense_variant	Exon 55 of 64		XP_016880204.1
MYO15A	XM_017024714.3	c.9434G>T	p.Arg3145Leu	missense_variant	Exon 54 of 63		XP_016880203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2	c.9494G>T	p.Arg3165Leu	missense_variant	Exon 57 of 66		NM_016239.4	ENSP00000495481.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461682 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;T;T;.;.;.;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.71	T;.;T;T;T;T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.1	.;M;M;.;.;.;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.4	.;N;.;.;.;D;.;.
REVEL	Benign	0.26
Sift	Benign	0.20	.;T;.;.;.;T;.;.
Sift4G	Uncertain	0.033	D;D;.;T;.;T;T;T
Polyphen		0.34	.;B;B;.;.;.;.;.
Vest4		0.39
MutPred		0.47		Loss of catalytic residue at R3165 (P = 0.0259);Loss of catalytic residue at R3165 (P = 0.0259);Loss of catalytic residue at R3165 (P = 0.0259);.;.;.;.;.;
MVP		0.67
ClinPred		0.29	T
GERP RS		2.1
Varity_R		0.070
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: -8

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18064738;