rs590722

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145809.2(MYH14):c.91C>A(p.Pro31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,547,002 control chromosomes in the GnomAD database, including 17,969 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1856 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16113 hom. )

Consequence

MYH14
NM_001145809.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.179

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00569883).

BP6

Variant 19-50210456-C-A is Benign according to our data. Variant chr19-50210456-C-A is described in ClinVar as [Benign]. Clinvar id is 44081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50210456-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 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.91C>A	p.Pro31Thr	missense_variant	2/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2 linkuse as main transcript	c.91C>A	p.Pro31Thr	missense_variant	2/42		NP_001070654.1
MYH14	NM_024729.4 linkuse as main transcript	c.91C>A	p.Pro31Thr	missense_variant	2/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 linkuse as main transcript	c.91C>A	p.Pro31Thr	missense_variant	2/43		NM_001145809.2	ENSP00000493594		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23147

AN:

152060

Hom.:

1854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.176

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.167

AC:

24215

AN:

145258

Hom.:

2094

AF XY:

0.170

AC XY:

13495

AN XY:

79556

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.143

Gnomad EAS exome

AF:

0.285

Gnomad SAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.150

AC:

209298

AN:

1394830

Hom.:

16113

Cov.:

AF XY:

0.152

AC XY:

104408

AN XY:

688820

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.152

AC:

23171

AN:

152172

Hom.:

1856

Cov.:

AF XY:

0.152

AC XY:

11347

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.143

Hom.:

377

Bravo

AF:

0.155

TwinsUK

AF:

0.146

AC:

541

ALSPAC

AF:

0.150

AC:

580

ESP6500AA

AF:

0.108

AC:

319

ESP6500EA

AF:

0.116

AC:

784

ExAC

AF:

0.119

AC:

12355

Asia WGS

AF:

0.217

AC:

751

AN:

3470

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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Pro31Thr in Exon 02 of MYH14: This variant is not expected to have clinical sign ificance because it has been identified in 11.1% (573/5178) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs590722). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 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. -

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 12, 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

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.095

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

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.77

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

MetaRNN

Benign

0.0057

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L;L;L;.;L;.;L

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.0

.;N;N;.;.;.;.;.

REVEL

Benign

0.094

Sift

Uncertain

0.022

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

Sift4G

Benign

0.12

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

Polyphen

0.063

B;B;B;B;.;B;.;B

Vest4

0.072

MPC

0.81

ClinPred

0.0045

GERP RS

2.2

Varity_R

0.079

gMVP

0.31

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