Variant 17-10306547-G-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.5378C>T(p.Thr1793Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,614,010 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 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

MYH13
NM_003802.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

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=0.35785097).

BS2

High AC in GnomAd at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYH13	NM_003802.3 linkuse as main transcript	c.5378C>T	p.Thr1793Met	missense_variant	37/41	ENST00000252172.9
LOC107985004	XR_007065617.1 linkuse as main transcript	n.96-10951G>A		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3 linkuse as main transcript	n.96-10951G>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.5378C>T	p.Thr1793Met	missense_variant	37/41	1	NM_003802.3	P1
MYH13	ENST00000621918.1 linkuse as main transcript	c.5378C>T	p.Thr1793Met	missense_variant	35/39	1		P1
	ENST00000609088.1 linkuse as main transcript	n.95-10951G>A		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8 linkuse as main transcript	c.5378C>T	p.Thr1793Met	missense_variant	36/40	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251490

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000964

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Nov 08, 2022

The c.5378C>T (p.T1793M) 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 5378, causing the threonine (T) at amino acid position 1793 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.17

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.54

D;D;D

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.038

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Uncertain

0.41

MutationAssessor

Pathogenic

3.3

M;M;M

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Uncertain

0.75

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.27

B;B;B

Vest4

0.41

MutPred

0.48

Loss of phosphorylation at T1793 (P = 0.0547);Loss of phosphorylation at T1793 (P = 0.0547);Loss of phosphorylation at T1793 (P = 0.0547);

MVP

0.80

MPC

0.10

ClinPred

0.77

GERP RS

4.2

Varity_R

0.23

gMVP

0.60

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