rs12936065

Variant names:

• chr17-10366197-C-T
• rs12936065
• NM_003802.3:c.-12-1655G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003802.3(MYH13):​c.-12-1655G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,150 control chromosomes in the GnomAD database, including 13,080 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 0.40 (13080 hom., cov: 28)
• Consequence: MYH13 NM_003802.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 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.-12-1655G>A		intron	N/A	NP_003793.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH13	ENST00000252172.9	TSL:1 MANE Select	c.-12-1655G>A		intron	N/A	ENSP00000252172.4
	MYH13	ENST00000418404.8	TSL:5	c.-12-1655G>A		intron	N/A	ENSP00000404570.3
	MYHAS	ENST00000584139.2	TSL:3	n.440-39951C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.403 AC: 60922 AN: 151032 Hom.: 13081 Cov.: 28

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.403 AC: 60943 AN: 151150 Hom.: 13080 Cov.: 28 AF XY: 0.399 AC XY: 29461 AN XY: 73792

African (AFR) AF: 0.281 AC: 11568 AN: 41142

American (AMR) AF: 0.381 AC: 5777 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1637 AN: 3460

East Asian (EAS) AF: 0.244 AC: 1255 AN: 5136

South Asian (SAS) AF: 0.226 AC: 1085 AN: 4796

European-Finnish (FIN) AF: 0.513 AC: 5337 AN: 10410

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.486 AC: 32900 AN: 67754

Other (OTH) AF: 0.421 AC: 881 AN: 2094

Alfa AF: 0.455 Hom.: 45633

Bravo AF: 0.391

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.42
PhyloP100		-0.70
Mutation Taster		=100/0	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: rs12936065; hg19: chr17-10269514;