rs61734424

Variant names:

• chr19-50244276-T-C
• rs61734424
• NM_001145809.2:c.1149T>C

Variant summary

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

The NM_001145809.2(MYH14):​c.1149T>C​(p.Phe383Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,613,776 control chromosomes in the GnomAD database, including 2,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (415 hom., cov: 31)
  • Exomes 𝑓: 0.041 (2146 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.57

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 19-50244276-T-C is Benign according to our data. Variant chr19-50244276-T-C is described in ClinVar as [Benign]. Clinvar id is 44046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50244276-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.1149T>C	p.Phe383Phe	synonymous_variant	Exon 11 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.1149T>C	p.Phe383Phe	synonymous_variant	Exon 11 of 42		NP_001070654.1
MYH14	NM_024729.4	c.1125T>C	p.Phe375Phe	synonymous_variant	Exon 10 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.1149T>C	p.Phe383Phe	synonymous_variant	Exon 11 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9124 AN: 152062 Hom.: 409 Cov.: 31

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0328

Gnomad OTH AF: 0.0621

GnomAD3 exomes AF: 0.0653 AC: 16232 AN: 248718 Hom.: 1121 AF XY: 0.0581 AC XY: 7846 AN XY: 134986

Gnomad AFR exome AF: 0.0873

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.0515

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0348

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0333

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0412 AC: 60244 AN: 1461596 Hom.: 2146 Cov.: 32 AF XY: 0.0402 AC XY: 29256 AN XY: 727096

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.0520

Gnomad4 EAS exome AF: 0.00207

Gnomad4 SAS exome AF: 0.0362

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.0322

Gnomad4 OTH exome AF: 0.0450

GnomAD4 genome AF: 0.0602 AC: 9154 AN: 152180 Hom.: 415 Cov.: 31 AF XY: 0.0629 AC XY: 4676 AN XY: 74398

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0328

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0432 Hom.: 103

Bravo AF: 0.0655

Asia WGS AF: 0.0330 AC: 113 AN: 3478

EpiCase AF: 0.0338

EpiControl AF: 0.0307

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Aug 31, 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

Phe383Phe in Exon 11 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 8.1% (292/3598) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs61734424). -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.74
CADD	Benign	0.70
DANN	Benign	0.41

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: rs61734424; hg19: chr19-50747533; COSMIC: COSV51835389;