2-196163280-G-T

Variant names:

• chr2-196163280-G-T
• NM_004226.4:c.104C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004226.4(STK17B):​c.104C>A​(p.Thr35Lys) 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: 2.91
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16291809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK17B	NM_004226.4	c.104C>A	p.Thr35Lys	missense_variant	Exon 2 of 8	ENST00000263955.9	NP_004217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK17B	ENST00000263955.9	c.104C>A	p.Thr35Lys	missense_variant	Exon 2 of 8	1	NM_004226.4	ENSP00000263955.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.104C>A (p.T35K) alteration is located in exon 2 (coding exon 1) of the STK17B gene. This alteration results from a C to A substitution at nucleotide position 104, causing the threonine (T) at amino acid position 35 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.0065	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.072	T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.034
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.87	.;D;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.85	L;L;.
PhyloP100		2.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.010	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.75	T;T;T
Sift4G	Benign	0.91	T;T;.
Polyphen		0.33	B;B;.
Vest4		0.43
MutPred		0.52		Gain of ubiquitination at T35 (P = 0.0408);Gain of ubiquitination at T35 (P = 0.0408);Gain of ubiquitination at T35 (P = 0.0408);
MVP		0.69
MPC		0.54
ClinPred		0.29	T
GERP RS		5.4
Varity_R		0.34
gMVP		0.68
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

hg19: chr2-197028004;