5-172082425-G-C

Position:

• chr5-172082425-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005990.4(STK10):​c.1890C>G​(p.Asp630Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: STK10 NM_005990.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0810

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059854656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK10	NM_005990.4	c.1890C>G	p.Asp630Glu	missense_variant	12/19	ENST00000176763.10
STK10	XM_047417627.1	c.1500C>G	p.Asp500Glu	missense_variant	9/16
STK10	XM_047417628.1	c.1341C>G	p.Asp447Glu	missense_variant	11/18
STK10	XM_047417629.1	c.1206C>G	p.Asp402Glu	missense_variant	10/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK10	ENST00000176763.10	c.1890C>G	p.Asp630Glu	missense_variant	12/19	1	NM_005990.4	P1
STK10	ENST00000522879.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.1890C>G (p.D630E) alteration is located in exon 12 (coding exon 12) of the STK10 gene. This alteration results from a C to G substitution at nucleotide position 1890, causing the aspartic acid (D) at amino acid position 630 to be replaced by a glutamic acid (E). 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	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.64
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0050	N
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.017	B
Vest4		0.21
MutPred		0.12		Loss of MoRF binding (P = 0.1026);
MVP		0.15
MPC		0.30
ClinPred		0.14	T
GERP RS		3.3
Varity_R		0.055
gMVP		0.037

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

Other links and lift over

dbSNP: rs563669946; hg19: chr5-171509429;