1-36341843-G-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.1220C>A(p.Ala407Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,461,366 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

STK40
NM_001282547.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Publications

0 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=0.07025355).

BS2

High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK40	NM_001282547.2 link	c.1220C>A	p.Ala407Glu	missense_variant	Exon 11 of 11	ENST00000373132.4	NP_001269476.1	Q8N2I9-1
STK40	NM_001282546.2 link	c.1235C>A	p.Ala412Glu	missense_variant	Exon 11 of 11		NP_001269475.1	Q8N2I9-4
STK40	NM_032017.3 link	c.1220C>A	p.Ala407Glu	missense_variant	Exon 12 of 12		NP_114406.1	Q8N2I9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STK40	ENST00000373132.4 link	c.1220C>A	p.Ala407Glu	missense_variant	Exon 11 of 11	1	NM_001282547.2	ENSP00000362224.4	Q8N2I9-1
STK40	ENST00000373130.7 link	c.1235C>A	p.Ala412Glu	missense_variant	Exon 11 of 11	1		ENSP00000362222.3	Q8N2I9-4
STK40	ENST00000373129.7 link	c.1220C>A	p.Ala407Glu	missense_variant	Exon 12 of 12	1		ENSP00000362221.3	Q8N2I9-1
STK40	ENST00000359297.6 link	c.*1356C>A		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000352245.2	Q8N2I9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000319

AC:

AN:

250474

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461366

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000325

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5546

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111934

Other (OTH)

AF:

0.0000166

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1220C>A (p.A407E) alteration is located in exon 12 (coding exon 10) of the STK40 gene. This alteration results from a C to A substitution at nucleotide position 1220, causing the alanine (A) at amino acid position 407 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

0.25

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.3

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.012

T;.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.81

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

.;T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N

PhyloP100

4.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.10

N;N;N

REVEL

Benign

0.093

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.021

B;B;B

Vest4

0.059

MutPred

0.29

Loss of MoRF binding (P = 0.0322);.;Loss of MoRF binding (P = 0.0322);

MVP

0.23

MPC

0.45

ClinPred

0.017

GERP RS

1.3

Varity_R

0.037

gMVP

0.24

Mutation Taster

=100/0

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

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1-36341843-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over