chr17-10325498-A-G

Variant names:

• chr17-10325498-A-G
• rs1859999
• NM_003802.3:c.2692-1234T>C

Variant summary

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

The NM_003802.3(MYH13):​c.2692-1234T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,846 control chromosomes in the GnomAD database, including 27,077 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 0.59 (27077 hom., cov: 31)
• Consequence: MYH13 NM_003802.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 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.2692-1234T>C		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.2692-1234T>C		intron	N/A	ENSP00000252172.4
	MYH13	ENST00000621918.1	TSL:1	c.2692-1234T>C		intron	N/A	ENSP00000480864.1
	MYH13	ENST00000418404.8	TSL:5	c.2692-1234T>C		intron	N/A	ENSP00000404570.3

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89937 AN: 151728 Hom.: 27069 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.593 AC: 89987 AN: 151846 Hom.: 27077 Cov.: 31 AF XY: 0.587 AC XY: 43561 AN XY: 74180

African (AFR) AF: 0.519 AC: 21458 AN: 41384

American (AMR) AF: 0.586 AC: 8953 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1840 AN: 3466

East Asian (EAS) AF: 0.392 AC: 2017 AN: 5144

South Asian (SAS) AF: 0.446 AC: 2144 AN: 4812

European-Finnish (FIN) AF: 0.649 AC: 6826 AN: 10522

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.659 AC: 44764 AN: 67940

Other (OTH) AF: 0.580 AC: 1219 AN: 2100

Alfa AF: 0.626 Hom.: 47095

Bravo AF: 0.588

Asia WGS AF: 0.438 AC: 1523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.28
PhyloP100		-0.55
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: rs1859999; hg19: chr17-10228815;