rs200485394

Positions:

chr19-50307053-C-T

Variant summary

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

The NM_001145809.2(MYH14):c.5683C>T(p.Arg1895Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,547,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

MYH14
NM_001145809.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.63

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=0.043082774).

BP6

Variant 19-50307053-C-T is Benign according to our data. Variant chr19-50307053-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 504622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000578 (88/152340) while in subpopulation AFR AF= 0.00178 (74/41572). AF 95% confidence interval is 0.00145. There are 0 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH14	NM_001145809.2 linkuse as main transcript	c.5683C>T	p.Arg1895Cys	missense_variant	41/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2 linkuse as main transcript	c.5584C>T	p.Arg1862Cys	missense_variant	40/42		NP_001070654.1
MYH14	NM_024729.4 linkuse as main transcript	c.5560C>T	p.Arg1854Cys	missense_variant	39/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 linkuse as main transcript	c.5683C>T	p.Arg1895Cys	missense_variant	41/43		NM_001145809.2	ENSP00000493594		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000304

AC:

AN:

154470

Hom.:

AF XY:

0.000282

AC XY:

AN XY:

81700

show subpopulations

Gnomad AFR exome

AF:

0.00263

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000232

Gnomad OTH exome

AF:

0.000460

GnomAD4 exome

AF:

0.000222

AC:

310

AN:

1395414

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

149

AN XY:

688360

show subpopulations

Gnomad4 AFR exome

AF:

0.00235

Gnomad4 AMR exome

AF:

0.000420

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.000179

Gnomad4 OTH exome

AF:

0.000363

GnomAD4 genome

AF:

0.000578

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000199

Hom.:

Bravo

AF:

0.000888

ESP6500AA

AF:

0.00149

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000175

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2021	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 22, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 05, 2019

The p.Arg1895Cys variant in MYH14 is classified as benign because it has been identified in 0.2% (33/16692) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). It has also been identified by our laboratory in an unaffected parent of a child with hearing loss. ACMG/AMP criteria applied: BA1. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.75

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

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

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

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.043

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

MetaSVM

Uncertain

0.38

MutationAssessor

Uncertain

2.2

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

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.8

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

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.012

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

Polyphen

1.0

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

Vest4

0.53

MVP

0.72

MPC

0.76

ClinPred

0.11

GERP RS

4.4

Varity_R

0.19

gMVP

0.40

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