NM_001145809.2:c.483G>A

Variant names:

Variant summary

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

The NM_001145809.2(MYH14):c.483G>A(p.Met161Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00899 in 1,614,010 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 94 hom. )

Consequence

MYH14
NM_001145809.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 5.79

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=0.013709426).

BP6

Variant 19-50217692-G-A is Benign according to our data. Variant chr19-50217692-G-A is described in ClinVar as [Benign]. Clinvar id is 44073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50217692-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0152 (2321/152332) while in subpopulation AFR AF= 0.0293 (1220/41576). AF 95% confidence interval is 0.028. There are 27 homozygotes in gnomad4. There are 1130 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2321 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2 link	c.483G>A	p.Met161Ile	missense_variant	Exon 3 of 43	ENST00000642316.2	NP_001139281.1	Q7Z406-2A1L2Z2B3KWH4
MYH14	NM_001077186.2 link	c.483G>A	p.Met161Ile	missense_variant	Exon 3 of 42		NP_001070654.1	Q7Z406-6B3KWH4
MYH14	NM_024729.4 link	c.483G>A	p.Met161Ile	missense_variant	Exon 3 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.483G>A	p.Met161Ile	missense_variant	Exon 3 of 43		NM_001145809.2	ENSP00000493594.1		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2315

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0293

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00783

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00969

AC:

2415

AN:

249292

Hom.:

AF XY:

0.00916

AC XY:

1239

AN XY:

135230

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.00976

Gnomad ASJ exome

AF:

0.0262

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000654

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.00851

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.00834

AC:

12189

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

5817

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.00770

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.0152

AC:

2321

AN:

152332

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1130

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0293

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.00783

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0166

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.0274

AC:

119

ESP6500EA

AF:

0.00772

AC:

ExAC

AF:

0.00968

AC:

1174

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00771

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 24, 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

- -

not specified

Benign:3

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Met161Ile in Exon 03 of MYH14: This variant is not expected to have clinical sig nificance because it has been identified in 2.8% (103/3676) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs34773557). -

Nov 17, 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. -

Sep 22, 2017

Eurofins Ntd Llc (ga)

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

Pathogenic

0.76

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

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

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

.;D;D;.;D;T;.

MetaRNN

Benign

0.014

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

MetaSVM

Uncertain

0.14

MutationAssessor

Uncertain

2.1

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

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.6

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

REVEL

Uncertain

0.51

Sift

Uncertain

0.016

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

Sift4G

Benign

0.11

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

Polyphen

0.71

P;P;P;P;.;P;P

Vest4

0.52

MutPred

0.49

Loss of ubiquitination at K165 (P = 0.074);Loss of ubiquitination at K165 (P = 0.074);Loss of ubiquitination at K165 (P = 0.074);Loss of ubiquitination at K165 (P = 0.074);Loss of ubiquitination at K165 (P = 0.074);Loss of ubiquitination at K165 (P = 0.074);Loss of ubiquitination at K165 (P = 0.074);

MVP

0.76

MPC

1.2

ClinPred

0.014

GERP RS

4.6

Varity_R

0.28

gMVP

0.58

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