rs1859999

Positions:

• chr17-10325498-A-G
• chr17-10325498-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH13	NM_003802.3	c.2692-1234T>C		intron_variant		ENST00000252172.9	NP_003793.2
LOC107985004	XR_007065617.1	n.681+4986A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH13	ENST00000252172.9	c.2692-1234T>C		intron_variant		1	NM_003802.3	ENSP00000252172	P1
MYH13	ENST00000621918.1	c.2692-1234T>C		intron_variant		1		ENSP00000480864	P1
	ENST00000577743.1	n.246+531A>G		intron_variant, non_coding_transcript_variant		2
MYH13	ENST00000418404.8	c.2692-1234T>C		intron_variant		5		ENSP00000404570	P1

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

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.580

Alfa AF: 0.633 Hom.: 34303

Bravo AF: 0.588

Asia WGS AF: 0.438 AC: 1523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.28

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: rs1859999; hg19: chr17-10228815;