rs77895476

Positions:

chr19-50252698-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001145809.2(MYH14):c.1890C>T(p.Val630=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,601,110 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 136 hom., cov: 32)

Exomes 𝑓: 0.015 ( 351 hom. )

Consequence

MYH14
NM_001145809.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.40

Variant links:

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]

MYH14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 19-50252698-C-T is Benign according to our data. Variant chr19-50252698-C-T is described in ClinVar as [Benign]. Clinvar id is 44051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50252698-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYH14	NM_001145809.2 linkuse as main transcript	c.1890C>T	p.Val630=	synonymous_variant	16/43	ENST00000642316.2
MYH14	NM_001077186.2 linkuse as main transcript	c.1890C>T	p.Val630=	synonymous_variant	16/42
MYH14	NM_024729.4 linkuse as main transcript	c.1866C>T	p.Val622=	synonymous_variant	15/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2 linkuse as main transcript	c.1890C>T	p.Val630=	synonymous_variant	16/43		NM_001145809.2		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

4905

AN:

152152

Hom.:

136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0715

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0227

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.0963

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0229

AC:

5232

AN:

228332

Hom.:

141

AF XY:

0.0213

AC XY:

2620

AN XY:

123216

show subpopulations

Gnomad AFR exome

AF:

0.0750

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.0982

Gnomad SAS exome

AF:

0.00939

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0208

GnomAD4 exome

AF:

0.0150

AC:

21676

AN:

1448840

Hom.:

351

Cov.:

AF XY:

0.0145

AC XY:

10428

AN XY:

719462

show subpopulations

Gnomad4 AFR exome

AF:

0.0758

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.0203

Gnomad4 EAS exome

AF:

0.0810

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.0160

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.0222

GnomAD4 genome

AF:

0.0322

AC:

4907

AN:

152270

Hom.:

136

Cov.:

AF XY:

0.0323

AC XY:

2406

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0714

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.0959

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.0186

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0213

Hom.:

Bravo

AF:

0.0357

Asia WGS

AF:

0.0490

AC:

172

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Val630Val in Exon 16 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 6.6% (243/3694) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs77895476). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 23, 2018	- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.67

CADD

Benign

0.19

DANN

Benign

0.93

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over