8-98770798-A-T

Position:

• chr8-98770798-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000419617.7(STK3):​c.108-3427T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,984 control chromosomes in the GnomAD database, including 29,100 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 0.61 (29100 hom., cov: 31)
• Consequence: STK3 ENST00000419617.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

STK3 (HGNC:11406): (serine/threonine kinase 3) This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK3	NM_006281.4	c.108-3427T>A		intron_variant		ENST00000419617.7	NP_006272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK3	ENST00000419617.7	c.108-3427T>A		intron_variant		1	NM_006281.4	ENSP00000390500	P1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93392 AN: 151866 Hom.: 29091 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.615 AC: 93433 AN: 151984 Hom.: 29100 Cov.: 31 AF XY: 0.615 AC XY: 45681 AN XY: 74288

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.623

Alfa AF: 0.519 Hom.: 1503

Bravo AF: 0.601

Asia WGS AF: 0.610 AC: 2119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.85

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: rs7827435; hg19: chr8-99783026;