rs8077577

Variant names:

• chr17-18161416-C-T
• rs8077577
• NM_016239.4:c.9486C>T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_016239.4(MYO15A):​c.9486C>T​(p.Asp3162Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,840 control chromosomes in the GnomAD database, including 29,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2857 hom., cov: 33)
  • Exomes 𝑓: 0.18 (26167 hom.)
• Consequence: MYO15A NM_016239.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.83

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 17-18161416-C-T is Benign according to our data. Variant chr17-18161416-C-T is described in ClinVar as [Benign]. Clinvar id is 45774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-18161416-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15A	NM_016239.4	c.9486C>T	p.Asp3162Asp	synonymous_variant	Exon 57 of 66	ENST00000647165.2	NP_057323.3
MYO15A	XM_017024715.3	c.9489C>T	p.Asp3163Asp	synonymous_variant	Exon 55 of 64		XP_016880204.1
MYO15A	XM_017024714.3	c.9426C>T	p.Asp3142Asp	synonymous_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.9486C>T	p.Asp3162Asp	synonymous_variant	Exon 57 of 66		NM_016239.4	ENSP00000495481.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28706 AN: 152020 Hom.: 2844 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.170 AC: 42355 AN: 249316 Hom.: 4068 AF XY: 0.176 AC XY: 23755 AN XY: 135302

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.00679

Gnomad SAS exome AF: 0.180

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.184 AC: 269367 AN: 1461702 Hom.: 26167 Cov.: 33 AF XY: 0.186 AC XY: 134930 AN XY: 727168

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.00461

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.189 AC: 28767 AN: 152138 Hom.: 2857 Cov.: 33 AF XY: 0.184 AC XY: 13670 AN XY: 74378

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.212

Alfa AF: 0.194 Hom.: 2108

Bravo AF: 0.193

Asia WGS AF: 0.108 AC: 375 AN: 3478

EpiCase AF: 0.209

EpiControl AF: 0.218

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Oct 16, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Asp3162Asp in Exon 57 of MYO15A: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 20.8% (1435/6896) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs8077577). -

Autosomal recessive nonsyndromic hearing loss 3 Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.62
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 0

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

Publications

LitVar

Other links and lift over

dbSNP: rs8077577; hg19: chr17-18064730; COSMIC: COSV52758423; COSMIC: COSV52758423;