Variant 17-10303494-C-T 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.5471G>A(p.Arg1824Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,550 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 1 hom. )

Consequence

MYH13
NM_003802.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.659

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=0.34621704).

BS2

High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYH13	NM_003802.3 linkuse as main transcript	c.5471G>A	p.Arg1824Gln	missense_variant	38/41	ENST00000252172.9
LOC107985004	XR_007065617.1 linkuse as main transcript	n.95+11581C>T		intron_variant, non_coding_transcript_variant
LOC107985004	XR_001752791.3 linkuse as main transcript	n.95+11581C>T		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.5471G>A	p.Arg1824Gln	missense_variant	38/41	1	NM_003802.3	P1
MYH13	ENST00000621918.1 linkuse as main transcript	c.5471G>A	p.Arg1824Gln	missense_variant	36/39	1		P1
	ENST00000609088.1 linkuse as main transcript	n.94+11581C>T		intron_variant, non_coding_transcript_variant		4
MYH13	ENST00000418404.8 linkuse as main transcript	c.5471G>A	p.Arg1824Gln	missense_variant	37/40	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000923

AC:

AN:

249246

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461430

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000263

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.0000662

AC:

EpiCase

AF:

0.0000545

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

Feb 03, 2022

The c.5471G>A (p.R1824Q) alteration is located in exon 38 (coding exon 36) of the MYH13 gene. This alteration results from a G to A substitution at nucleotide position 5471, causing the arginine (R) at amino acid position 1824 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.32

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

T;T;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.056

FATHMM_MKL

Benign

0.39

M_CAP

Benign

0.019

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.5

H;H;H

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.33

Sift4G

Uncertain

0.016

D;D;D

Polyphen

0.97

D;D;D

Vest4

0.32

MVP

0.67

MPC

0.11

ClinPred

0.57

GERP RS

1.9

Varity_R

0.28

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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