rs61734424

Positions:

chr19-50244276-T-C

Variant summary

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

The NM_001145809.2(MYH14):c.1149T>C(p.Phe383=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.57

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=-0.74).

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/exons	MANE	Protein
MYH14	NM_001145809.2 linkuse as main transcript	c.1149T>C	p.Phe383=	synonymous_variant	11/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2 linkuse as main transcript	c.1149T>C	p.Phe383=	synonymous_variant	11/42		NP_001070654.1
MYH14	NM_024729.4 linkuse as main transcript	c.1125T>C	p.Phe375=	synonymous_variant	10/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 linkuse as main transcript	c.1149T>C	p.Phe383=	synonymous_variant	11/43		NM_001145809.2	ENSP00000493594		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9124

AN:

152062

Hom.:

409

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0402

AC XY:

29256

AN XY:

727096

show subpopulations

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.:

AF XY:

0.0629

AC XY:

4676

AN XY:

74398

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 31, 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	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). -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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

-0.74

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

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