rs61734424

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001145809.2(MYH14):c.1149T>C(p.Phe383Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,613,776 control chromosomes in the GnomAD database, including 2,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 415 hom., cov: 31)

Exomes 𝑓: 0.041 ( 2146 hom. )

Consequence

MYH14
NM_001145809.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.57

Publications

6 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 19-50244276-T-C is Benign according to our data. Variant chr19-50244276-T-C is described in ClinVar as Benign. ClinVar VariationId is 44046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MYH14	NM_001145809.2 link	c.1149T>C	p.Phe383Phe	synonymous_variant	Exon 11 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2 link	c.1149T>C	p.Phe383Phe	synonymous_variant	Exon 11 of 42		NP_001070654.1
MYH14	NM_024729.4 link	c.1125T>C	p.Phe375Phe	synonymous_variant	Exon 10 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 link	c.1149T>C	p.Phe383Phe	synonymous_variant	Exon 11 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9124

AN:

152062

Hom.:

409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0871

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0328

Gnomad OTH

AF:

0.0621

GnomAD2 exomes

AF:

0.0653

AC:

16232

AN:

248718

AF XY:

0.0581

show subpopulations

Gnomad AFR exome

AF:

0.0873

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.0515

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0572

GnomAD4 exome

AF:

0.0412

AC:

60244

AN:

1461596

Hom.:

2146

Cov.:

AF XY:

0.0402

AC XY:

29256

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.0833

AC:

2788

AN:

33476

American (AMR)

AF:

0.191

AC:

8529

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0520

AC:

1358

AN:

26132

East Asian (EAS)

AF:

0.00207

AC:

AN:

39696

South Asian (SAS)

AF:

0.0362

AC:

3126

AN:

86258

European-Finnish (FIN)

AF:

0.106

AC:

5672

AN:

53358

Middle Eastern (MID)

AF:

0.0307

AC:

177

AN:

5768

European-Non Finnish (NFE)

AF:

0.0322

AC:

35795

AN:

1111820

Other (OTH)

AF:

0.0450

AC:

2717

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3147

6294

9441

12588

15735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1490

2980

4470

5960

7450

<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:

0.0602

AC:

9154

AN:

152180

Hom.:

415

Cov.:

AF XY:

0.0629

AC XY:

4676

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0873

AC:

3625

AN:

41528

American (AMR)

AF:

0.113

AC:

1723

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

158

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5168

South Asian (SAS)

AF:

0.0315

AC:

152

AN:

4826

European-Finnish (FIN)

AF:

0.104

AC:

1106

AN:

10588

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0328

AC:

2232

AN:

68006

Other (OTH)

AF:

0.0615

AC:

130

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

428

856

1284

1712

2140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0436

Hom.:

148

Bravo

AF:

0.0655

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

EpiCase

AF:

0.0338

EpiControl

AF:

0.0307

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Phe383Phe in Exon 11 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 8.1% (292/3598) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs61734424). -

Aug 31, 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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:1

Jan 13, 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

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.70

(source)

DANN

Benign

0.41

PhyloP100

-1.6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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