rs556541366

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145809.2(MYH14):c.1301A>G(p.Tyr434Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000713 in 1,613,440 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 1 hom. )

Consequence

MYH14
NM_001145809.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.85

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019899458).

BP6

Variant 19-50247094-A-G is Benign according to our data. Variant chr19-50247094-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 179004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000138 (21/152242) while in subpopulation EAS AF= 0.00367 (19/5184). AF 95% confidence interval is 0.0024. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2 link	c.1301A>G	p.Tyr434Cys	missense_variant	Exon 12 of 43	ENST00000642316.2	NP_001139281.1	Q7Z406-2A1L2Z2B3KWH4
MYH14	NM_001077186.2 link	c.1301A>G	p.Tyr434Cys	missense_variant	Exon 12 of 42		NP_001070654.1	Q7Z406-6B3KWH4
MYH14	NM_024729.4 link	c.1277A>G	p.Tyr426Cys	missense_variant	Exon 11 of 41		NP_079005.3	Q7Z406-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 link	c.1301A>G	p.Tyr434Cys	missense_variant	Exon 12 of 43		NM_001145809.2	ENSP00000493594.1		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000254

AC:

AN:

247914

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

134592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00338

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.0000643

AC:

AN:

1461198

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00207

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000138

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.000297

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 25, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

not specified

Benign:1

Jun 04, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Tyr434Cys in exon 12 of MYH14: This variant is not expected to have clinical s ignificance because it has been identified in 0.4% (36/8364) of East Asian chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs556541366). -

Autosomal dominant nonsyndromic hearing loss 4A;C3280556:Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

Benign:1

Aug 10, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

.;.;D;.;D;.;D

Eigen

Benign

0.075

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.79

.;T;T;.;T;T;.

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.020

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.041

MutationAssessor

Uncertain

2.2

.;.;M;.;.;.;M

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.9

.;D;D;.;.;.;.

REVEL

Uncertain

0.52

Sift

Uncertain

0.010

.;D;D;.;.;.;.

Sift4G

Uncertain

0.010

D;D;D;.;D;D;D

Polyphen

0.42

B;B;P;B;.;B;P

Vest4

0.76

MutPred

0.48

.;.;Gain of ubiquitination at K429 (P = 0.0726);.;.;.;Gain of ubiquitination at K429 (P = 0.0726);

MVP

0.74

MPC

1.4

ClinPred

0.18

GERP RS

2.6

Varity_R

0.29

gMVP

0.56

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