Variant 5-172055635-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005990.4(STK10):c.2479A>G(p.Ile827Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000495 in 1,413,778 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: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

STK10
NM_005990.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.93

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38744614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK10	NM_005990.4 linkuse as main transcript	c.2479A>G	p.Ile827Val	missense_variant	16/19	ENST00000176763.10	NP_005981.3	O94804
STK10	XM_047417627.1 linkuse as main transcript	c.2089A>G	p.Ile697Val	missense_variant	13/16		XP_047273583.1
STK10	XM_047417628.1 linkuse as main transcript	c.1930A>G	p.Ile644Val	missense_variant	15/18		XP_047273584.1
STK10	XM_047417629.1 linkuse as main transcript	c.1795A>G	p.Ile599Val	missense_variant	14/17		XP_047273585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK10	ENST00000176763.10 linkuse as main transcript	c.2479A>G	p.Ile827Val	missense_variant	16/19	1	NM_005990.4	ENSP00000176763.5		O94804
STK10	ENST00000520476.1 linkuse as main transcript	c.295A>G	p.Ile99Val	missense_variant	3/7	2		ENSP00000428806.1		H0YB71

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000356

AC:

AN:

224988

Hom.:

AF XY:

0.0000491

AC XY:

AN XY:

122112

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000218

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000386

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000948

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000495

AC:

AN:

1413778

Hom.:

Cov.:

AF XY:

0.00000715

AC XY:

AN XY:

699592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.22e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

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

Nov 19, 2022

The c.2479A>G (p.I827V) alteration is located in exon 16 (coding exon 16) of the STK10 gene. This alteration results from a A to G substitution at nucleotide position 2479, causing the isoleucine (I) at amino acid position 827 to be replaced by a valine (V). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.022

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

2.9

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.87

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Benign

0.072

Polyphen

1.0

Vest4

0.60

MutPred

0.17

Loss of methylation at K822 (P = 0.1157);

MVP

0.60

MPC

0.93

ClinPred

0.64

GERP RS

5.5

Varity_R

0.46

gMVP

0.11

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