Variant 17-10309305-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The ENST00000252172.9(MYH13):c.5098G>A(p.Glu1700Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MYH13
ENST00000252172.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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 -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.825

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH13	NM_003802.3 linkuse as main transcript	c.5098G>A	p.Glu1700Lys	missense_variant	35/41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_007065617.1 linkuse as main transcript	n.96-8193C>T		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3 linkuse as main transcript	n.96-8193C>T		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.5098G>A	p.Glu1700Lys	missense_variant	35/41	1	NM_003802.3	ENSP00000252172	P1
MYH13	ENST00000621918.1 linkuse as main transcript	c.5098G>A	p.Glu1700Lys	missense_variant	33/39	1		ENSP00000480864	P1
	ENST00000609088.1 linkuse as main transcript	n.95-8193C>T		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8 linkuse as main transcript	c.5098G>A	p.Glu1700Lys	missense_variant	34/40	5		ENSP00000404570	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152266

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248252

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000478

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000577

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

Aug 15, 2023

The c.5098G>A (p.E1700K) alteration is located in exon 35 (coding exon 33) of the MYH13 gene. This alteration results from a G to A substitution at nucleotide position 5098, causing the glutamic acid (E) at amino acid position 1700 to be replaced by a lysine (K). 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

Benign

0.26

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

T;T;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

.;D;.

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

0.76

MutationAssessor

Pathogenic

3.8

H;H;H

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.8

.;.;D

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0010

.;.;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.94

P;P;P

Vest4

0.72

MutPred

0.73

Gain of ubiquitination at E1700 (P = 0.0128);Gain of ubiquitination at E1700 (P = 0.0128);Gain of ubiquitination at E1700 (P = 0.0128);

MVP

0.85

MPC

0.23

ClinPred

0.98

GERP RS

3.5

Varity_R

0.57

gMVP

0.81

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