Genetic Variant MYH13:p.Ala1808Val (chr17-10306502-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003802.3(MYH13):c.5423C>T(p.Ala1808Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

MYH13
NM_003802.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

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:

ENSG00000273388 (HGNC:):

ENSG00000273388 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH13	NM_003802.3 link	c.5423C>T	p.Ala1808Val	missense_variant	Exon 37 of 41	ENST00000252172.9	NP_003793.2	Q9UKX3
LOC107985004	XR_001752791.3 link	n.96-10996G>A		intron_variant	Intron 1 of 4
LOC107985004	XR_007065617.1 link	n.96-10996G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH13	ENST00000252172.9 link	c.5423C>T	p.Ala1808Val	missense_variant	Exon 37 of 41	1	NM_003802.3	ENSP00000252172.4	Q9UKX3
MYH13	ENST00000621918.1 link	c.5423C>T	p.Ala1808Val	missense_variant	Exon 35 of 39	1		ENSP00000480864.1	Q9UKX3
MYH13	ENST00000418404.8 link	c.5423C>T	p.Ala1808Val	missense_variant	Exon 36 of 40	5		ENSP00000404570.3	Q9UKX3
ENSG00000273388	ENST00000609088.1 link	n.95-10996G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251476

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000217

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000723

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000230

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5423C>T (p.A1808V) alteration is located in exon 37 (coding exon 35) of the MYH13 gene. This alteration results from a C to T substitution at nucleotide position 5423, causing the alanine (A) at amino acid position 1808 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

0.41

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.46

T;T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;.

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Uncertain

0.52

MutationAssessor

Uncertain

2.6

M;M;M

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.0

.;.;D

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

.;.;D

Sift4G

Benign

0.084

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.75

MVP

0.88

MPC

0.26

ClinPred

0.61

GERP RS

4.2

Varity_R

0.68

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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