rs751042475

Variant names:

• chr2-196137598-T-C
• rs751042475
• NM_004226.4:c.968A>G

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.968A>G​(p.Asp323Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STK17B NM_004226.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17
• Publications: 1 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=0.09732184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK17B	NM_004226.4	c.968A>G	p.Asp323Gly	missense_variant	Exon 8 of 8	ENST00000263955.9	NP_004217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK17B	ENST00000263955.9	c.968A>G	p.Asp323Gly	missense_variant	Exon 8 of 8	1	NM_004226.4	ENSP00000263955.4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251408 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461788 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74374

African (AFR) AF: 0.000145 AC: 6 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.968A>G (p.D323G) alteration is located in exon 8 (coding exon 7) of the STK17B gene. This alteration results from a A to G substitution at nucleotide position 968, causing the aspartic acid (D) at amino acid position 323 to be replaced by a glycine (G). 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	0.072
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.81	L;L
PhyloP100		5.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.032
Sift	Benign	0.14	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.10	B;B
Vest4		0.18
MVP		0.71
MPC		0.64
ClinPred		0.20	T
GERP RS		4.8
Varity_R		0.18
gMVP		0.38
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs751042475; hg19: chr2-197002322;