17-10328100-C-T

Position:

• chr17-10328100-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003802.3(MYH13):​c.2457G>A​(p.Gln819Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,613,528 control chromosomes in the GnomAD database, including 33,039 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3464 hom., cov: 31)
  • Exomes 𝑓: 0.19 (29575 hom.)
• Consequence: MYH13 NM_003802.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728

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]

ENSG00000264067 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH13	NM_003802.3	c.2457G>A	p.Gln819Gln	synonymous_variant	22/41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_007065617.1	n.681+7588C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.2457G>A	p.Gln819Gln	synonymous_variant	22/41	1	NM_003802.3	ENSP00000252172.4
MYH13	ENST00000621918.1	c.2457G>A	p.Gln819Gln	synonymous_variant	20/39	1		ENSP00000480864.1
MYH13	ENST00000418404.8	c.2457G>A	p.Gln819Gln	synonymous_variant	21/40	5		ENSP00000404570.3
ENSG00000264067	ENST00000577743.1	n.246+3133C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30751 AN: 151896 Hom.: 3457 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.231 AC: 57808 AN: 250028 Hom.: 7859 AF XY: 0.229 AC XY: 30971 AN XY: 135480

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.518

Gnomad SAS exome AF: 0.289

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.190 AC: 278348 AN: 1461512 Hom.: 29575 Cov.: 33 AF XY: 0.193 AC XY: 140355 AN XY: 727052

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.203 AC: 30791 AN: 152016 Hom.: 3464 Cov.: 31 AF XY: 0.207 AC XY: 15386 AN XY: 74308

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.195

Alfa AF: 0.186 Hom.: 1999

Bravo AF: 0.204

Asia WGS AF: 0.351 AC: 1222 AN: 3478

EpiCase AF: 0.172

EpiControl AF: 0.174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: -31

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2277644; hg19: chr17-10231417; COSMIC: COSV52843848;