17-10356123-T-C

Variant names:

• chr17-10356123-T-C
• rs4791980
• NM_003802.3:c.739-976A>G

Variant summary

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

The NM_003802.3(MYH13):​c.739-976A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,030 control chromosomes in the GnomAD database, including 23,025 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 0.55 (23025 hom., cov: 32)
• Consequence: MYH13 NM_003802.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 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.739-976A>G		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.739-976A>G		intron	N/A	ENSP00000252172.4
	MYH13	ENST00000621918.1	TSL:1	c.739-976A>G		intron	N/A	ENSP00000480864.1
	MYH13	ENST00000418404.8	TSL:5	c.739-976A>G		intron	N/A	ENSP00000404570.3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83359 AN: 151914 Hom.: 22987 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.549 AC: 83456 AN: 152030 Hom.: 23025 Cov.: 32 AF XY: 0.551 AC XY: 40926 AN XY: 74302

African (AFR) AF: 0.554 AC: 22952 AN: 41458

American (AMR) AF: 0.546 AC: 8325 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1782 AN: 3472

East Asian (EAS) AF: 0.630 AC: 3256 AN: 5166

South Asian (SAS) AF: 0.536 AC: 2585 AN: 4826

European-Finnish (FIN) AF: 0.559 AC: 5896 AN: 10556

Middle Eastern (MID) AF: 0.559 AC: 162 AN: 290

European-Non Finnish (NFE) AF: 0.542 AC: 36873 AN: 67986

Other (OTH) AF: 0.527 AC: 1110 AN: 2106

Alfa AF: 0.541 Hom.: 25829

Bravo AF: 0.550

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.60
PhyloP100		1.5
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: rs4791980; hg19: chr17-10259440;