1-36348759-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001282547.2(STK40):c.680G>A(p.Gly227Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000104 in 1,610,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

STK40
NM_001282547.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.87

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.090082765).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK40	NM_001282547.2 link	c.680G>A	p.Gly227Glu	missense_variant	Exon 7 of 11	ENST00000373132.4	NP_001269476.1	Q8N2I9-1
STK40	NM_001282546.2 link	c.695G>A	p.Gly232Glu	missense_variant	Exon 7 of 11		NP_001269475.1	Q8N2I9-4
STK40	NM_032017.3 link	c.680G>A	p.Gly227Glu	missense_variant	Exon 8 of 12		NP_114406.1	Q8N2I9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STK40	ENST00000373132.4 link	c.680G>A	p.Gly227Glu	missense_variant	Exon 7 of 11	1	NM_001282547.2	ENSP00000362224.4	Q8N2I9-1
STK40	ENST00000373130.7 link	c.695G>A	p.Gly232Glu	missense_variant	Exon 7 of 11	1		ENSP00000362222.3	Q8N2I9-4
STK40	ENST00000373129.7 link	c.680G>A	p.Gly227Glu	missense_variant	Exon 8 of 12	1		ENSP00000362221.3	Q8N2I9-1
STK40	ENST00000359297.6 link	c.680G>A	p.Gly227Glu	missense_variant	Exon 6 of 9	2		ENSP00000352245.2	Q8N2I9-3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000531

AC:

AN:

244876

AF XY:

0.0000529

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000996

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

162

AN:

1458592

Hom.:

Cov.:

AF XY:

0.0000993

AC XY:

AN XY:

725220

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33372

American (AMR)

AF:

0.0000225

AC:

AN:

44402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39530

South Asian (SAS)

AF:

0.00

AC:

AN:

85472

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000143

AC:

159

AN:

1110510

Other (OTH)

AF:

0.0000166

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.680G>A (p.G227E) alteration is located in exon 8 (coding exon 6) of the STK40 gene. This alteration results from a G to A substitution at nucleotide position 680, causing the glycine (G) at amino acid position 227 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

0.089

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;T;.;T

Eigen

Benign

-0.048

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.91

D;.;D;D

M_CAP

Benign

0.0060

MetaRNN

Benign

0.090

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.41

N;N;.;N

PhyloP100

5.9

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.71

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.72

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.32

MVP

0.10

MPC

0.48

ClinPred

0.11

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.55

Mutation Taster

=69/31

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-36348759-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over