17-10328100-C-T

Variant names:

• chr17-10328100-C-T
• rs2277644
• NM_003802.3:c.2457G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985004 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003802.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	NM_003802.3	MANE Select	c.2457G>A	p.Gln819Gln	synonymous	Exon 22 of 41	NP_003793.2	Q9UKX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	ENST00000252172.9	TSL:1 MANE Select	c.2457G>A	p.Gln819Gln	synonymous	Exon 22 of 41	ENSP00000252172.4	Q9UKX3
	MYH13	ENST00000621918.1	TSL:1	c.2457G>A	p.Gln819Gln	synonymous	Exon 20 of 39	ENSP00000480864.1	Q9UKX3
	MYH13	ENST00000418404.8	TSL:5	c.2457G>A	p.Gln819Gln	synonymous	Exon 21 of 40	ENSP00000404570.3	Q9UKX3

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

GnomAD2 exomes AF: 0.231 AC: 57808 AN: 250028 AF XY: 0.229

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 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

African (AFR) AF: 0.205 AC: 6845 AN: 33460

American (AMR) AF: 0.262 AC: 11710 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 5431 AN: 26122

East Asian (EAS) AF: 0.488 AC: 19358 AN: 39680

South Asian (SAS) AF: 0.288 AC: 24840 AN: 86206

European-Finnish (FIN) AF: 0.187 AC: 10006 AN: 53416

Middle Eastern (MID) AF: 0.276 AC: 1592 AN: 5762

European-Non Finnish (NFE) AF: 0.168 AC: 186310 AN: 1111812

Other (OTH) AF: 0.203 AC: 12256 AN: 60388

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

African (AFR) AF: 0.206 AC: 8551 AN: 41432

American (AMR) AF: 0.217 AC: 3314 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3470

East Asian (EAS) AF: 0.509 AC: 2617 AN: 5142

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4822

European-Finnish (FIN) AF: 0.189 AC: 2004 AN: 10578

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11619 AN: 67968

Other (OTH) AF: 0.195 AC: 412 AN: 2114

Alfa AF: 0.184 Hom.: 2563

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		0.73
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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