chr2-196146016-C-A

Variant names:

• chr2-196146016-C-A
• rs1699567961
• NM_004226.4:c.375G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004226.4(STK17B):​c.375G>T​(p.Glu125Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK17B NM_004226.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0650
• Publications: 0 publications found

Genes affected

STK17B (HGNC:11396): (serine/threonine kinase 17b) Enables ATP binding activity and protein serine/threonine kinase activity. Involved in intracellular signal transduction; positive regulation of fibroblast apoptotic process; and protein phosphorylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03964168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK17B	NM_004226.4	c.375G>T	p.Glu125Asp	missense_variant	Exon 4 of 8	ENST00000263955.9	NP_004217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK17B	ENST00000263955.9	c.375G>T	p.Glu125Asp	missense_variant	Exon 4 of 8	1	NM_004226.4	ENSP00000263955.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.375G>T (p.E125D) alteration is located in exon 4 (coding exon 3) of the STK17B gene. This alteration results from a G to T substitution at nucleotide position 375, causing the glutamic acid (E) at amino acid position 125 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.67
DEOGEN2	Benign	0.053	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;N
PhyloP100		0.065
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	1.6	N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.47		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.38
MPC		0.38
ClinPred		0.29	T
GERP RS		2.0
Varity_R		0.069
gMVP		0.50
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs1699567961; hg19: chr2-197010740;