Variant chr17-10303278-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003802.3(MYH13):c.5585A>G(p.His1862Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,613,780 control chromosomes in the GnomAD database, including 9,690 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1164 hom., cov: 32)

Exomes 𝑓: 0.091 ( 8526 hom. )

Consequence

MYH13
NM_003802.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014390349).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH13	NM_003802.3 linkuse as main transcript	c.5585A>G	p.His1862Arg	missense_variant	39/41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_007065617.1 linkuse as main transcript	n.95+11365T>C		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3 linkuse as main transcript	n.95+11365T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYH13	ENST00000252172.9 linkuse as main transcript	c.5585A>G	p.His1862Arg	missense_variant	39/41	1	NM_003802.3	ENSP00000252172	P1
MYH13	ENST00000621918.1 linkuse as main transcript	c.5585A>G	p.His1862Arg	missense_variant	37/39	1		ENSP00000480864	P1
	ENST00000609088.1 linkuse as main transcript	n.94+11365T>C		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8 linkuse as main transcript	c.5585A>G	p.His1862Arg	missense_variant	38/40	5		ENSP00000404570	P1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16546

AN:

151958

Hom.:

1155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0738

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.0712

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0691

Gnomad OTH

AF:

0.0819

GnomAD3 exomes

AF:

0.125

AC:

31175

AN:

249804

Hom.:

2769

AF XY:

0.125

AC XY:

17004

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.0788

Gnomad EAS exome

AF:

0.337

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.0728

Gnomad NFE exome

AF:

0.0722

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.0912

AC:

133290

AN:

1461704

Hom.:

8526

Cov.:

AF XY:

0.0943

AC XY:

68583

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.0788

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.0715

Gnomad4 NFE exome

AF:

0.0705

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.109

AC:

16595

AN:

152076

Hom.:

1164

Cov.:

AF XY:

0.112

AC XY:

8331

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0738

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.0712

Gnomad4 NFE

AF:

0.0692

Gnomad4 OTH

AF:

0.0877

Alfa

AF:

0.0816

Hom.:

1124

Bravo

AF:

0.113

TwinsUK

AF:

0.0677

AC:

251

ALSPAC

AF:

0.0763

AC:

294

ESP6500AA

AF:

0.141

AC:

601

ESP6500EA

AF:

0.0685

AC:

584

ExAC

AF:

0.127

AC:

15349

Asia WGS

AF:

0.273

AC:

949

AN:

3478

EpiCase

AF:

0.0719

EpiControl

AF:

0.0732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.1

DANN

Benign

0.33

DEOGEN2

Benign

0.092

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.47

.;T;.

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

N;N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

2.6

.;.;N

REVEL

Benign

0.19

Sift

Benign

1.0

.;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.038

MPC

0.12

ClinPred

0.0037

GERP RS

0.54

Varity_R

0.046

gMVP

0.078

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over