rs16897122

chr8-98906757-A-G

Variant summary

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

The ENST00000523960.1(STK3):n.269-16855T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 152,170 control chromosomes in the GnomAD database, including 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 0.030 (100 hom., cov: 32)
• Consequence: STK3 ENST00000523960.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502

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 = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK3	NM_001256312.2	c.-206-16855T>C		intron_variant
STK3	XM_011517248.3	c.94-22923T>C		intron_variant
STK3	XM_011517252.4	c.94-22923T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK3	ENST00000523960.1	n.269-16855T>C		intron_variant, non_coding_transcript_variant		1
STK3	ENST00000519420.1	c.-78-22923T>C		intron_variant		4
STK3	ENST00000523601.5	c.-206-16855T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4539 AN: 152052 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00858

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0298 AC: 4538 AN: 152170 Hom.: 100 Cov.: 32 AF XY: 0.0290 AC XY: 2160 AN XY: 74402

Gnomad4 AFR AF: 0.00855

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0669

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.0471

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.0369 Hom.: 18

Bravo AF: 0.0275

Asia WGS AF: 0.0250 AC: 88 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	1.7
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16897122; hg19: chr8-99918985;