Variant rs2074877 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000252172.9(MYH13):c.3211A>G(p.Met1071Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,611,744 control chromosomes in the GnomAD database, including 302,694 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.61 ( 28747 hom., cov: 33)

Exomes 𝑓: 0.61 ( 273947 hom. )

Consequence

MYH13
ENST00000252172.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

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=2.289554E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 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.3211A>G	p.Met1071Val	missense_variant	25/41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_007065617.1 linkuse as main transcript	n.566T>C		non_coding_transcript_exon_variant	4/5
LOC107985004	XR_001752791.3 linkuse as main transcript	n.566T>C		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYH13	ENST00000252172.9 linkuse as main transcript	c.3211A>G	p.Met1071Val	missense_variant	25/41	1	NM_003802.3	ENSP00000252172	P1
MYH13	ENST00000621918.1 linkuse as main transcript	c.3211A>G	p.Met1071Val	missense_variant	23/39	1		ENSP00000480864	P1
	ENST00000577743.1 linkuse as main transcript	n.6T>C		non_coding_transcript_exon_variant	1/3	2
MYH13	ENST00000418404.8 linkuse as main transcript	c.3211A>G	p.Met1071Val	missense_variant	24/40	5		ENSP00000404570	P1

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

93177

AN:

152046

Hom.:

28712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.617

GnomAD3 exomes

AF:

0.595

AC:

146361

AN:

246104

Hom.:

44157

AF XY:

0.587

AC XY:

78337

AN XY:

133448

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.666

Gnomad ASJ exome

AF:

0.641

Gnomad EAS exome

AF:

0.438

Gnomad SAS exome

AF:

0.465

Gnomad FIN exome

AF:

0.583

Gnomad NFE exome

AF:

0.624

Gnomad OTH exome

AF:

0.609

GnomAD4 exome

AF:

0.610

AC:

890567

AN:

1459580

Hom.:

273947

Cov.:

AF XY:

0.605

AC XY:

439244

AN XY:

725954

show subpopulations

Gnomad4 AFR exome

AF:

0.630

Gnomad4 AMR exome

AF:

0.662

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.468

Gnomad4 FIN exome

AF:

0.589

Gnomad4 NFE exome

AF:

0.625

Gnomad4 OTH exome

AF:

0.602

GnomAD4 genome

AF:

0.613

AC:

93264

AN:

152164

Hom.:

28747

Cov.:

AF XY:

0.605

AC XY:

44994

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.637

Gnomad4 AMR

AF:

0.618

Gnomad4 ASJ

AF:

0.634

Gnomad4 EAS

AF:

0.438

Gnomad4 SAS

AF:

0.463

Gnomad4 FIN

AF:

0.575

Gnomad4 NFE

AF:

0.625

Gnomad4 OTH

AF:

0.615

Alfa

AF:

0.620

Hom.:

72638

Bravo

AF:

0.621

TwinsUK

AF:

0.636

AC:

2359

ALSPAC

AF:

0.620

AC:

2390

ESP6500AA

AF:

0.648

AC:

2418

ESP6500EA

AF:

0.630

AC:

5157

ExAC

AF:

0.591

AC:

71361

Asia WGS

AF:

0.488

AC:

1700

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.29

T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.70

.;T;.

MetaRNN

Benign

0.000023

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

0.91

P;P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.2

.;.;N

REVEL

Benign

0.23

Sift

Uncertain

0.017

.;.;D

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.087

MPC

0.097

ClinPred

0.0099

GERP RS

1.3

Varity_R

0.22

gMVP

0.28

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