rs16897122

Variant names:

• chr8-98906757-A-G
• rs16897122
• ENST00000523960.1:n.269-16855T>C

Variant summary

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

The ENST00000523960.1(STK3):​n.269-16855T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502
• Publications: 1 publications found

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]

MRPL57P7 (HGNC:29690): (mitochondrial ribosomal protein L57 pseudogene 7)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
STK3	NM_001256312.2	c.-206-16855T>C		intron_variant	Intron 1 of 12		NP_001243241.1
STK3	XM_017013756.2	c.94-22923T>C		intron_variant	Intron 1 of 12		XP_016869245.1
STK3	XM_011517248.3	c.94-22923T>C		intron_variant	Intron 1 of 11		XP_011515550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK3	ENST00000523960.1	n.269-16855T>C		intron_variant	Intron 1 of 2	1
STK3	ENST00000523601.5	c.-206-16855T>C		intron_variant	Intron 1 of 12	2		ENSP00000429744.1
STK3	ENST00000519420.1	c.-78-22923T>C		intron_variant	Intron 1 of 1	4		ENSP00000428295.1
MRPL57P7	ENST00000518583.1	n.-240T>C		upstream_gene_variant		6

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

African (AFR) AF: 0.00855 AC: 355 AN: 41520

American (AMR) AF: 0.0162 AC: 247 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0669 AC: 322 AN: 4810

European-Finnish (FIN) AF: 0.0149 AC: 158 AN: 10602

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3205 AN: 67996

Other (OTH) AF: 0.0242 AC: 51 AN: 2108

Alfa AF: 0.0362 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
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs16897122; hg19: chr8-99918985;