chr19-50293257-C-A

Variant names:

• chr19-50293257-C-A
• rs116035034
• NM_001145809.2:c.5281C>A

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.5281C>A​(p.Arg1761Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,608,748 control chromosomes in the GnomAD database, including 362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (206 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (156 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0780

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=-0.37).
• BP6: Variant 19-50293257-C-A is Benign according to our data. Variant chr19-50293257-C-A is described in ClinVar as [Benign]. Clinvar id is 178617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50293257-C-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.078 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.5281C>A	p.Arg1761Arg	synonymous_variant	Exon 38 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.5182C>A	p.Arg1728Arg	synonymous_variant	Exon 37 of 42		NP_001070654.1
MYH14	NM_024729.4	c.5158C>A	p.Arg1720Arg	synonymous_variant	Exon 36 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.5281C>A	p.Arg1761Arg	synonymous_variant	Exon 38 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3883 AN: 152086 Hom.: 206 Cov.: 32

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00638 AC: 1520 AN: 238226 Hom.: 71 AF XY: 0.00524 AC XY: 679 AN XY: 129662

Gnomad AFR exome AF: 0.0889

Gnomad AMR exome AF: 0.00496

Gnomad ASJ exome AF: 0.000616

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000309

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000566

Gnomad OTH exome AF: 0.00431

GnomAD4 exome AF: 0.00273 AC: 3982 AN: 1456544 Hom.: 156 Cov.: 32 AF XY: 0.00241 AC XY: 1748 AN XY: 723950

Gnomad4 AFR exome AF: 0.0883

Gnomad4 AMR exome AF: 0.00643

Gnomad4 ASJ exome AF: 0.000694

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000247

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000239

Gnomad4 OTH exome AF: 0.00675

GnomAD4 genome AF: 0.0255 AC: 3880 AN: 152204 Hom.: 206 Cov.: 32 AF XY: 0.0244 AC XY: 1816 AN XY: 74422

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00398 Hom.: 3

Bravo AF: 0.0301

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 23, 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

Arg1761Arg in Exon 38 of MYH14: 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 8.3% (284/3432) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs116035034). -

not provided Benign:3

Jan 15, 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

- -

May 23, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.37
CADD	Benign	11
DANN	Benign	0.57

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: rs116035034; hg19: chr19-50796514;