Variant 5-172044992-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005990.4(STK10):c.2797C>T(p.Arg933Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

STK10
NM_005990.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.339

Variant links:

Genes affected

STK10 (HGNC:11388): (serine/threonine kinase 10) This gene encodes a member of the Ste20 family of serine/threonine protein kinases, and is similar to several known polo-like kinase kinases. The protein can associate with and phosphorylate polo-like kinase 1, and overexpression of a kinase-dead version of the protein interferes with normal cell cycle progression. The kinase can also negatively regulate interleukin 2 expression in T-cells via the mitogen activated protein kinase kinase 1 pathway. [provided by RefSeq, Jul 2008]

STK10 links:

STK10 (HGNC:):

STK10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22326925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK10	NM_005990.4 linkuse as main transcript	c.2797C>T	p.Arg933Trp	missense_variant	19/19	ENST00000176763.10	NP_005981.3	O94804
STK10	XM_047417627.1 linkuse as main transcript	c.2407C>T	p.Arg803Trp	missense_variant	16/16		XP_047273583.1
STK10	XM_047417628.1 linkuse as main transcript	c.2248C>T	p.Arg750Trp	missense_variant	18/18		XP_047273584.1
STK10	XM_047417629.1 linkuse as main transcript	c.2113C>T	p.Arg705Trp	missense_variant	17/17		XP_047273585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STK10	ENST00000176763.10 linkuse as main transcript	c.2797C>T	p.Arg933Trp	missense_variant	19/19	1	NM_005990.4	ENSP00000176763.5	O94804
STK10	ENST00000520476.1 linkuse as main transcript	c.668C>T	p.Ala223Val	missense_variant	7/7	2		ENSP00000428806.1	H0YB71
STK10	ENST00000517360.1 linkuse as main transcript	n.303C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251414

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.2797C>T (p.R933W) alteration is located in exon 19 (coding exon 19) of the STK10 gene. This alteration results from a C to T substitution at nucleotide position 2797, causing the arginine (R) at amino acid position 933 to be replaced by a tryptophan (W). 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

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.097

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.81

M_CAP

Benign

0.058

MetaRNN

Benign

0.22

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.17

Sift

Uncertain

0.025

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.23

MutPred

0.23

Loss of MoRF binding (P = 0.0763);

MVP

0.68

MPC

0.83

ClinPred

0.75

GERP RS

3.7

Varity_R

0.15

gMVP

0.25

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over