rs61731838

Variant names:

• chr19-50250613-C-T
• rs61731838
• NM_001145809.2:c.1755C>T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001145809.2(MYH14):​c.1755C>T​(p.Gly585Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 1,613,792 control chromosomes in the GnomAD database, including 4,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (529 hom., cov: 32)
  • Exomes 𝑓: 0.066 (4074 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.293

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 19-50250613-C-T is Benign according to our data. Variant chr19-50250613-C-T is described in ClinVar as [Benign]. Clinvar id is 44050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50250613-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.293 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.1755C>T	p.Gly585Gly	synonymous_variant	Exon 15 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.1755C>T	p.Gly585Gly	synonymous_variant	Exon 15 of 42		NP_001070654.1
MYH14	NM_024729.4	c.1731C>T	p.Gly577Gly	synonymous_variant	Exon 14 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.1755C>T	p.Gly585Gly	synonymous_variant	Exon 15 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11023 AN: 152084 Hom.: 522 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0603

Gnomad OTH AF: 0.0856

GnomAD3 exomes AF: 0.0844 AC: 20990 AN: 248698 Hom.: 1425 AF XY: 0.0780 AC XY: 10539 AN XY: 135046

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.0756

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0405

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0853

GnomAD4 exome AF: 0.0659 AC: 96315 AN: 1461590 Hom.: 4074 Cov.: 31 AF XY: 0.0647 AC XY: 47036 AN XY: 727080

Gnomad4 AFR exome AF: 0.0676

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.0784

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0422

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.0602

Gnomad4 OTH exome AF: 0.0673

GnomAD4 genome AF: 0.0726 AC: 11053 AN: 152202 Hom.: 529 Cov.: 32 AF XY: 0.0747 AC XY: 5558 AN XY: 74402

Gnomad4 AFR AF: 0.0677

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0603

Gnomad4 OTH AF: 0.0847

Alfa AF: 0.0651 Hom.: 141

Bravo AF: 0.0749

Asia WGS AF: 0.0340 AC: 120 AN: 3478

EpiCase AF: 0.0622

EpiControl AF: 0.0588

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Aug 25, 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

Gly585Gly in Exon 15 of MYH14: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 6.9% (252/3668) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs61731838). -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autosomal dominant nonsyndromic hearing loss 4A Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	5.3
DANN	Benign	0.74

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: rs61731838; hg19: chr19-50753870; COSMIC: COSV51815796; COSMIC: COSV51815796;