Variant 19-50210397-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001145809.2(MYH14):c.32G>A(p.Arg11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000569 in 1,580,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. R11R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

MYH14
NM_001145809.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.26

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1961394).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH14	NM_001145809.2 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	2/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	2/42		NP_001070654.1
MYH14	NM_024729.4 linkuse as main transcript	c.32G>A	p.Arg11Gln	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.32G>A	p.Arg11Gln	missense_variant	2/43		NM_001145809.2	ENSP00000493594		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000560

AC:

AN:

1428806

Hom.:

Cov.:

AF XY:

0.00000423

AC XY:

AN XY:

709086

show subpopulations

Gnomad4 AFR exome

AF:

0.0000648

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000456

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

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:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MYH14-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2024

The MYH14 c.32G>A variant is predicted to result in the amino acid substitution p.Arg11Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

0.0081

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

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

Eigen

Benign

0.000088

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.89

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

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.20

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

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.2

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

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.33

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

REVEL

Uncertain

0.33

Sift

Uncertain

0.013

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

Sift4G

Pathogenic

0.0

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

Polyphen

0.49

P;P;B;P;.;P;.;B

Vest4

0.25

MutPred

0.29

Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);

MVP

0.50

MPC

0.54

ClinPred

0.20

GERP RS

4.3

Varity_R

0.13

gMVP

0.48

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