8-98408547-A-C

Position:

• chr8-98408547-A-C

Variant summary

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

The XM_047422133.1(STK3):​c.1424-20300T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,172 control chromosomes in the GnomAD database, including 2,711 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 0.15 (2711 hom., cov: 33)
• Consequence: STK3 XM_047422133.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK3	XM_047422133.1	c.1424-20300T>G		intron_variant
STK3	XR_007060752.1	n.1572-20300T>G		intron_variant, non_coding_transcript_variant
STK3	XR_007060753.1	n.1572-20300T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK3	ENST00000517832.1	n.484-7034T>G		intron_variant, non_coding_transcript_variant		3
STK3	ENST00000649151.1	n.428-20300T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22159 AN: 152056 Hom.: 2710 Cov.: 33

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.146 AC: 22153 AN: 152172 Hom.: 2711 Cov.: 33 AF XY: 0.150 AC XY: 11182 AN XY: 74400

Gnomad4 AFR AF: 0.0343

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.180

Alfa AF: 0.126 Hom.: 438

Bravo AF: 0.168

Asia WGS AF: 0.268 AC: 929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4130405; hg19: chr8-99420775;