Variant 1-36355363-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001282547.2(STK40):c.413G>T(p.Cys138Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STK40
NM_001282547.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53

Variant links:

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 links:

STK40 (HGNC:):

STK40 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.413G>T	p.Cys138Phe	missense_variant	5/11	ENST00000373132.4	NP_001269476.1	Q8N2I9-1
STK40	NM_001282546.2 linkuse as main transcript	c.428G>T	p.Cys143Phe	missense_variant	5/11		NP_001269475.1	Q8N2I9-4
STK40	NM_032017.3 linkuse as main transcript	c.413G>T	p.Cys138Phe	missense_variant	6/12		NP_114406.1	Q8N2I9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK40	ENST00000373132.4 linkuse as main transcript	c.413G>T	p.Cys138Phe	missense_variant	5/11	1	NM_001282547.2	ENSP00000362224.4		Q8N2I9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Mar 20, 2024

The c.413G>T (p.C138F) alteration is located in exon 6 (coding exon 4) of the STK40 gene. This alteration results from a G to T substitution at nucleotide position 413, causing the cysteine (C) at amino acid position 138 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

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

0.97

DEOGEN2

Benign

0.17

.;T;.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;.;D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.69

D;D;D;D

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.53

N;N;.;N

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.36

T;T;D;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.99

D;D;D;D

Vest4

0.91

MutPred

0.61

Loss of catalytic residue at L139 (P = 0.0118);Loss of catalytic residue at L139 (P = 0.0118);.;Loss of catalytic residue at L139 (P = 0.0118);

MVP

0.43

MPC

0.85

ClinPred

0.95

GERP RS

5.9

Varity_R

0.67

gMVP

0.75

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

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