1-36358256-G-A

Position:

• chr1-36358256-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001282547.2(STK40):​c.325C>T​(p.His109Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK40 NM_001282547.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.49

Genes affected

STK40 (HGNC:21373): (serine/threonine kinase 40) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to act upstream of or within several processes, including glycogen metabolic process; lung development; and respiratory system process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

STK40 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK40	NM_001282547.2	c.325C>T	p.His109Tyr	missense_variant	4/11	ENST00000373132.4	NP_001269476.1
STK40	NM_001282546.2	c.340C>T	p.His114Tyr	missense_variant	4/11		NP_001269475.1
STK40	NM_032017.3	c.325C>T	p.His109Tyr	missense_variant	5/12		NP_114406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK40	ENST00000373132.4	c.325C>T	p.His109Tyr	missense_variant	4/11	1	NM_001282547.2	ENSP00000362224.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Nov 10, 2024

The c.325C>T (p.H109Y) alteration is located in exon 5 (coding exon 3) of the STK40 gene. This alteration results from a C to T substitution at nucleotide position 325, causing the histidine (H) at amino acid position 109 to be replaced by a tyrosine (Y). 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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.97	D;.;D;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.9	L;L;.;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.29
Sift	Benign	0.074	T;T;D;T
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		0.021	B;D;D;D
Vest4		0.85
MutPred		0.52		Loss of disorder (P = 0.062);Loss of disorder (P = 0.062);.;Loss of disorder (P = 0.062);
MVP		0.45
MPC		1.2
ClinPred		0.96	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-36823857;