rs373462792

Variant names:

• chr17-18157209-C-A
• rs373462792
• NM_016239.4:c.8767C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-18157209-C-A
• chr17-18157209-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016239.4(MYO15A):​c.8767C>A​(p.Arg2923Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000756 in 1,455,986 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: 0.0000076 (0 hom.)
• Consequence: MYO15A NM_016239.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15A	NM_016239.4	c.8767C>A	p.Arg2923Arg	synonymous_variant	Exon 50 of 66	ENST00000647165.2	NP_057323.3
MYO15A	XM_017024715.3	c.8770C>A	p.Arg2924Arg	synonymous_variant	Exon 48 of 64		XP_016880204.1
MYO15A	XM_017024714.3	c.8707C>A	p.Arg2903Arg	synonymous_variant	Exon 47 of 63		XP_016880203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2	c.8767C>A	p.Arg2923Arg	synonymous_variant	Exon 50 of 66		NM_016239.4	ENSP00000495481.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1455986 Hom.: 0 Cov.: 32 AF XY: 0.00000691 AC XY: 5 AN XY: 723756

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33298

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44092

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26000

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39354

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 85218

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52812

Gnomad4 NFE exome AF: 0.00000992 AC: 11 AN: 1109372

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60080

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	7.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: 21

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

Publications

LitVar

Other links and lift over

dbSNP: rs373462792; hg19: chr17-18060523;