chr5-172057384-G-C

Position:

• chr5-172057384-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005990.4(STK10):​c.2302C>G​(p.Leu768Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK10 NM_005990.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

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 (HGNC:):

ACMG classification

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=0.38851026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK10	NM_005990.4	c.2302C>G	p.Leu768Val	missense_variant	15/19	ENST00000176763.10	NP_005981.3
STK10	XM_047417627.1	c.1912C>G	p.Leu638Val	missense_variant	12/16		XP_047273583.1
STK10	XM_047417628.1	c.1753C>G	p.Leu585Val	missense_variant	14/18		XP_047273584.1
STK10	XM_047417629.1	c.1618C>G	p.Leu540Val	missense_variant	13/17		XP_047273585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK10	ENST00000176763.10	c.2302C>G	p.Leu768Val	missense_variant	15/19	1	NM_005990.4	ENSP00000176763.5
STK10	ENST00000520476.1	c.118C>G	p.Leu40Val	missense_variant	2/7	2		ENSP00000428806.1
STK10	ENST00000519269.1	n.147C>G		non_coding_transcript_exon_variant	2/2	4
STK10	ENST00000523615.1	n.582C>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 31, 2024

The c.2302C>G (p.L768V) alteration is located in exon 15 (coding exon 15) of the STK10 gene. This alteration results from a C to G substitution at nucleotide position 2302, causing the leucine (L) at amino acid position 768 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	Benign	0.23
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.047	D
Polyphen		0.98	D
Vest4		0.39
MutPred		0.21		Gain of methylation at K763 (P = 0.0664);
MVP		0.47
MPC		1.0
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.45
gMVP		0.32

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: chr5-171484388;