Variant 17-10301618-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003802.3(MYH13):c.5753A>T(p.Glu1918Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

MYH13
NM_003802.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.93

Variant links:

Genes affected

MYH13 (HGNC:7571): (myosin heavy chain 13) Predicted to enable microfilament motor activity. Predicted to be involved in muscle contraction. Predicted to act upstream of or within cellular response to starvation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MYH13 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2964084).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYH13	NM_003802.3 linkuse as main transcript	c.5753A>T	p.Glu1918Val	missense_variant	40/41	ENST00000252172.9
LOC107985004	XR_007065617.1 linkuse as main transcript	n.95+9705T>A		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3 linkuse as main transcript	n.95+9705T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MYH13	ENST00000252172.9 linkuse as main transcript	c.5753A>T	p.Glu1918Val	missense_variant	40/41	1	NM_003802.3	P1
MYH13	ENST00000621918.1 linkuse as main transcript	c.5753A>T	p.Glu1918Val	missense_variant	38/39	1		P1
	ENST00000609088.1 linkuse as main transcript	n.94+9705T>A		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8 linkuse as main transcript	c.5753A>T	p.Glu1918Val	missense_variant	39/40	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

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

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251208

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000957

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2021

The c.5753A>T (p.E1918V) alteration is located in exon 40 (coding exon 38) of the MYH13 gene. This alteration results from a A to T substitution at nucleotide position 5753, causing the glutamic acid (E) at amino acid position 1918 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

D;D;D

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

.;D;.

M_CAP

Benign

0.046

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Pathogenic

0.88

MutationAssessor

Pathogenic

4.3

H;H;H

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.2

.;.;D

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.92

MutPred

0.56

Loss of ubiquitination at K1923 (P = 0.0213);Loss of ubiquitination at K1923 (P = 0.0213);Loss of ubiquitination at K1923 (P = 0.0213);

MVP

0.82

MPC

0.54

ClinPred

0.75

GERP RS

3.8

Varity_R

0.67

gMVP

0.45

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