19-50286559-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001145809.2(MYH14):c.4617T>G(p.Arg1539Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,611,776 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

MYH14
NM_001145809.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.357

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006118804).

BP6

Variant 19-50286559-T-G is Benign according to our data. Variant chr19-50286559-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 505306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.357 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000697 (106/152102) while in subpopulation AFR AF= 0.00251 (104/41482). AF 95% confidence interval is 0.00212. There are 1 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2 link	c.4617T>G	p.Arg1539Arg	synonymous_variant	Exon 34 of 43	ENST00000642316.2	NP_001139281.1	Q7Z406-2A1L2Z2B3KWH4
MYH14	NM_001077186.2 link	c.4518T>G	p.Arg1506Arg	synonymous_variant	Exon 33 of 42		NP_001070654.1	Q7Z406-6B3KWH4
MYH14	NM_024729.4 link	c.4494T>G	p.Arg1498Arg	synonymous_variant	Exon 32 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.4617T>G	p.Arg1539Arg	synonymous_variant	Exon 34 of 43		NM_001145809.2	ENSP00000493594.1		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.000684

AC:

104

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000186

AC:

AN:

242336

Hom.:

AF XY:

0.000189

AC XY:

AN XY:

132004

show subpopulations

Gnomad AFR exome

AF:

0.00273

Gnomad AMR exome

AF:

0.000118

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:

0.00

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000740

AC:

108

AN:

1459674

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

725858

show subpopulations

Gnomad4 AFR exome

AF:

0.00281

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000697

AC:

106

AN:

152102

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00251

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.000937

ESP6500AA

AF:

0.00264

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 16, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 19, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Arg1539Arg in exon 34 of MYH14: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. In addition, it has been identified in 0.3 7% (26/7080) of African chromosomes by the Exome Aggregation Consortium (ExAC, h ttp://exac.broadinstitute.org; dbSNP rs375866139). -

MYH14-related disorder

Benign:1

Feb 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.42

DANN

Benign

0.71

DEOGEN2

Benign

0.041

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0061

Sift4G

Benign

0.38

Vest4

0.12

MVP

0.62

GERP RS

-9.1

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