rs3740232

Variant names:

• chr10-26173861-G-A
• rs3740232
• NM_017433.5:c.3597G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-26173861-G-A
• chr10-26173861-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017433.5(MYO3A):​c.3597G>A​(p.Glu1199Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,613,704 control chromosomes in the GnomAD database, including 96,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8126 hom., cov: 32)
  • Exomes 𝑓: 0.35 (88235 hom.)
• Consequence: MYO3A NM_017433.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.243

Genes affected

MYO3A (HGNC:7601): (myosin IIIA) The protein encoded by this gene belongs to the myosin superfamily. Myosins are actin-dependent motor proteins and are categorized into conventional myosins (class II) and unconventional myosins (classes I and III through XV) based on their variable C-terminal cargo-binding domains. Class III myosins, such as this one, have a kinase domain N-terminal to the conserved N-terminal motor domains and are expressed in photoreceptors. The protein encoded by this gene plays an important role in hearing in humans. Three different recessive, loss of function mutations in the encoded protein have been shown to cause nonsyndromic progressive hearing loss. Expression of this gene is highly restricted, with the strongest expression in retina and cochlea. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-26173861-G-A is Benign according to our data. Variant chr10-26173861-G-A is described in ClinVar as [Benign]. Clinvar id is 45808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-26173861-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.243 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.3597G>A	p.Glu1199Glu	synonymous_variant	Exon 30 of 35	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.3597G>A	p.Glu1199Glu	synonymous_variant	Exon 30 of 35		NM_017433.5	ENSP00000495965.1
MYO3A	ENST00000543632.5	c.1777-37982G>A		intron_variant	Intron 16 of 16	1		ENSP00000445909.1
MYO3A	ENST00000647478.1	n.*1393+3322G>A		intron_variant	Intron 27 of 29			ENSP00000493932.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48918 AN: 151966 Hom.: 8128 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.326

GnomAD3 exomes AF: 0.343 AC: 85835 AN: 250344 Hom.: 14992 AF XY: 0.350 AC XY: 47479 AN XY: 135502

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.354

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.420

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.346 AC: 505288 AN: 1461620 Hom.: 88235 Cov.: 48 AF XY: 0.349 AC XY: 253405 AN XY: 727090

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.322 AC: 48924 AN: 152084 Hom.: 8126 Cov.: 32 AF XY: 0.326 AC XY: 24202 AN XY: 74328

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.327

Alfa AF: 0.341 Hom.: 17282

Bravo AF: 0.305

Asia WGS AF: 0.369 AC: 1280 AN: 3478

EpiCase AF: 0.354

EpiControl AF: 0.348

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Glu1199Glu in Exon 30 of MYO3A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 34.1% (2393/7020) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs3740232). -

Autosomal recessive nonsyndromic hearing loss 30 Benign:2

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. -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.83
CADD	Benign	0.67
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3740232; hg19: chr10-26462790; COSMIC: COSV56323746;