chr1-36341972-G-A

Position:

chr1-36341972-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001282547.2(STK40):c.1091C>T(p.Ala364Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

STK40
NM_001282547.2 missense, splice_region

Scores

Splicing: ADA: 0.00001080

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039195985).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK40	NM_001282547.2 linkuse as main transcript	c.1091C>T	p.Ala364Val	missense_variant, splice_region_variant	11/11	ENST00000373132.4	NP_001269476.1	Q8N2I9-1
STK40	NM_001282546.2 linkuse as main transcript	c.1106C>T	p.Ala369Val	missense_variant, splice_region_variant	11/11		NP_001269475.1	Q8N2I9-4
STK40	NM_032017.3 linkuse as main transcript	c.1091C>T	p.Ala364Val	missense_variant, splice_region_variant	12/12		NP_114406.1	Q8N2I9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STK40	ENST00000373132.4 linkuse as main transcript	c.1091C>T	p.Ala364Val	missense_variant, splice_region_variant	11/11	1	NM_001282547.2	ENSP00000362224.4	Q8N2I9-1
STK40	ENST00000373130.7 linkuse as main transcript	c.1106C>T	p.Ala369Val	missense_variant, splice_region_variant	11/11	1		ENSP00000362222.3	Q8N2I9-4
STK40	ENST00000373129.7 linkuse as main transcript	c.1091C>T	p.Ala364Val	missense_variant, splice_region_variant	12/12	1		ENSP00000362221.3	Q8N2I9-1
STK40	ENST00000359297 linkuse as main transcript	c.*1227C>T		3_prime_UTR_variant	9/9	2		ENSP00000352245.2	Q8N2I9-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152266

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000207

AC:

AN:

241692

Hom.:

AF XY:

0.0000380

AC XY:

AN XY:

131596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000933

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1459046

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725642

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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

Apr 23, 2024

The c.1091C>T (p.A364V) alteration is located in exon 12 (coding exon 10) of the STK40 gene. This alteration results from a C to T substitution at nucleotide position 1091, causing the alanine (A) at amino acid position 364 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

0.074

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.011

T;.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.67

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

.;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

N;.;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.60

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.083

MutPred

0.20

Gain of methylation at K365 (P = 0.0405);.;Gain of methylation at K365 (P = 0.0405);

MVP

0.18

MPC

0.37

ClinPred

0.022

GERP RS

3.0

Varity_R

0.018

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000011

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: -5

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