rs590722

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P31R) has been classified as Uncertain significance.

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

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 4A
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 44081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein
MYH14	NM_001145809.2 link	c.91C>A	p.Pro31Thr	missense_variant	Exon 2 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2 link	c.91C>A	p.Pro31Thr	missense_variant	Exon 2 of 42		NP_001070654.1
MYH14	NM_024729.4 link	c.91C>A	p.Pro31Thr	missense_variant	Exon 2 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 link	c.91C>A	p.Pro31Thr	missense_variant	Exon 2 of 43		NM_001145809.2	ENSP00000493594.1

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

GnomAD2 exomes

AF:

0.167

AC:

24215

AN:

145258

AF XY:

0.170

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 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

African (AFR)

AF:

0.160

AC:

4872

AN:

30432

American (AMR)

AF:

0.150

AC:

5350

AN:

35774

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

3562

AN:

24740

East Asian (EAS)

AF:

0.221

AC:

7798

AN:

35362

South Asian (SAS)

AF:

0.191

AC:

15128

AN:

79274

European-Finnish (FIN)

AF:

0.127

AC:

5989

AN:

47260

Middle Eastern (MID)

AF:

0.144

AC:

811

AN:

5632

European-Non Finnish (NFE)

AF:

0.145

AC:

156831

AN:

1078738

Other (OTH)

AF:

0.155

AC:

8957

AN:

57618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

10643

21286

31928

42571

53214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5826

11652

17478

23304

29130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23171

AN:

152172

Hom.:

1856

Cov.:

AF XY:

0.152

AC XY:

11347

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.157

AC:

6530

AN:

41524

American (AMR)

AF:

0.160

AC:

2454

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

468

AN:

3468

East Asian (EAS)

AF:

0.239

AC:

1235

AN:

5174

South Asian (SAS)

AF:

0.200

AC:

967

AN:

4826

European-Finnish (FIN)

AF:

0.119

AC:

1261

AN:

10594

Middle Eastern (MID)

AF:

0.179

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.144

AC:

9778

AN:

67978

Other (OTH)

AF:

0.147

AC:

311

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

987

1975

2962

3950

4937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.149

Hom.:

694

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

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

-0.18

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

PromoterAI

-0.038

Neutral

(source)

Varity_R

0.079

gMVP

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over