rs2240579

Variant names:

• chr17-10333148-G-A
• rs2240579
• NM_003802.3:c.2100C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-10333148-G-A
• chr17-10333148-G-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003802.3(MYH13):​c.2100C>T​(p.Asn700Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,550,794 control chromosomes in the GnomAD database, including 291,432 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 0.51 (21905 hom., cov: 33)
  • Exomes 𝑓: 0.61 (269527 hom.)
• Consequence: MYH13 NM_003802.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-2.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	NM_003802.3	MANE Select	c.2100C>T	p.Asn700Asn	synonymous	Exon 19 of 41	NP_003793.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	ENST00000252172.9	TSL:1 MANE Select	c.2100C>T	p.Asn700Asn	synonymous	Exon 19 of 41	ENSP00000252172.4
	MYH13	ENST00000621918.1	TSL:1	c.2100C>T	p.Asn700Asn	synonymous	Exon 17 of 39	ENSP00000480864.1
	MYH13	ENST00000418404.8	TSL:5	c.2100C>T	p.Asn700Asn	synonymous	Exon 18 of 40	ENSP00000404570.3

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77891 AN: 152034 Hom.: 21906 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.517

GnomAD2 exomes AF: 0.558 AC: 86807 AN: 155548 AF XY: 0.560

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.383

Gnomad FIN exome AF: 0.635

Gnomad NFE exome AF: 0.647

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.614 AC: 859045 AN: 1398642 Hom.: 269527 Cov.: 52 AF XY: 0.611 AC XY: 421343 AN XY: 689878

African (AFR) AF: 0.250 AC: 7909 AN: 31596

American (AMR) AF: 0.560 AC: 19999 AN: 35720

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13218 AN: 25182

East Asian (EAS) AF: 0.396 AC: 14156 AN: 35742

South Asian (SAS) AF: 0.464 AC: 36777 AN: 79218

European-Finnish (FIN) AF: 0.630 AC: 31019 AN: 49258

Middle Eastern (MID) AF: 0.469 AC: 2668 AN: 5690

European-Non Finnish (NFE) AF: 0.649 AC: 700048 AN: 1078248

Other (OTH) AF: 0.573 AC: 33251 AN: 57988

GnomAD4 genome AF: 0.512 AC: 77904 AN: 152152 Hom.: 21905 Cov.: 33 AF XY: 0.510 AC XY: 37930 AN XY: 74374

African (AFR) AF: 0.272 AC: 11297 AN: 41542

American (AMR) AF: 0.549 AC: 8399 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1817 AN: 3466

East Asian (EAS) AF: 0.388 AC: 2006 AN: 5170

South Asian (SAS) AF: 0.444 AC: 2142 AN: 4822

European-Finnish (FIN) AF: 0.641 AC: 6784 AN: 10580

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43634 AN: 67976

Other (OTH) AF: 0.517 AC: 1089 AN: 2108

Alfa AF: 0.584 Hom.: 16704

Bravo AF: 0.497

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.78
DANN	Benign	0.89
PhyloP100		-2.0
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240579; hg19: chr17-10236465; COSMIC: COSV52823120;