chr19-50250613-C-T

Position:

chr19-50250613-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001145809.2(MYH14):c.1755C>T(p.Gly585=) 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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.293

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:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein
MYH14	NM_001145809.2 linkuse as main transcript	c.1755C>T	p.Gly585=	synonymous_variant	15/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2 linkuse as main transcript	c.1755C>T	p.Gly585=	synonymous_variant	15/42		NP_001070654.1
MYH14	NM_024729.4 linkuse as main transcript	c.1731C>T	p.Gly577=	synonymous_variant	14/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 linkuse as main transcript	c.1755C>T	p.Gly585=	synonymous_variant	15/43		NM_001145809.2	ENSP00000493594		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11023

AN:

152084

Hom.:

522

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0647

AC XY:

47036

AN XY:

727080

show subpopulations

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.:

AF XY:

0.0747

AC XY:

5558

AN XY:

74402

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	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). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 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	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

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

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

-0.24

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

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