rs2240579

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH13	NM_003802.3	c.2100C>T	p.Asn700Asn	synonymous_variant	19/41	ENST00000252172.9	NP_003793.2
LOC107985004	XR_007065617.1	n.682-7916G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.2100C>T	p.Asn700Asn	synonymous_variant	19/41	1	NM_003802.3	ENSP00000252172.4
MYH13	ENST00000621918.1	c.2100C>T	p.Asn700Asn	synonymous_variant	17/39	1		ENSP00000480864.1
MYH13	ENST00000418404.8	c.2100C>T	p.Asn700Asn	synonymous_variant	18/40	5		ENSP00000404570.3
ENSG00000264067	ENST00000577743.1	n.247-7916G>A		intron_variant		2

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

GnomAD3 exomes AF: 0.558 AC: 86807 AN: 155548 Hom.: 25118 AF XY: 0.560 AC XY: 46056 AN XY: 82312

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 SAS exome AF: 0.466

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

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.560

Gnomad4 ASJ exome AF: 0.525

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.573

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

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.517

Alfa AF: 0.590 Hom.: 14717

Bravo AF: 0.497

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.78
DANN	Benign	0.89

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

Other links and lift over

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