5-172054603-C-A

Position:

• chr5-172054603-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005990.4(STK10):​c.2618G>T​(p.Cys873Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK10 NM_005990.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK10	NM_005990.4	c.2618G>T	p.Cys873Phe	missense_variant	17/19	ENST00000176763.10
STK10	XM_047417627.1	c.2228G>T	p.Cys743Phe	missense_variant	14/16
STK10	XM_047417628.1	c.2069G>T	p.Cys690Phe	missense_variant	16/18
STK10	XM_047417629.1	c.1934G>T	p.Cys645Phe	missense_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK10	ENST00000176763.10	c.2618G>T	p.Cys873Phe	missense_variant	17/19	1	NM_005990.4	P1
STK10	ENST00000520476.1	c.437G>T	p.Cys146Phe	missense_variant	4/7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jul 26, 2021

The c.2618G>T (p.C873F) alteration is located in exon 17 (coding exon 17) of the STK10 gene. This alteration results from a G to T substitution at nucleotide position 2618, causing the cysteine (C) at amino acid position 873 to be replaced by a phenylalanine (F). 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	0.46
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.099	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.011	D
Sift4G	Benign	0.49	T
Polyphen		1.0	D
Vest4		0.85
MutPred		0.31		Gain of MoRF binding (P = 0.0693);
MVP		0.56
MPC		1.3
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.79
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-171481607;