Variant 1-36358276-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001282547.2(STK40):c.305C>T(p.Thr102Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000986 in 1,602,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 1 hom. )

Consequence

STK40
NM_001282547.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14918298).

BS2

High AC in GnomAd at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STK40	NM_001282547.2 linkuse as main transcript	c.305C>T	p.Thr102Met	missense_variant	4/11	ENST00000373132.4
STK40	NM_001282546.2 linkuse as main transcript	c.320C>T	p.Thr107Met	missense_variant	4/11
STK40	NM_032017.3 linkuse as main transcript	c.305C>T	p.Thr102Met	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK40	ENST00000373132.4 linkuse as main transcript	c.305C>T	p.Thr102Met	missense_variant	4/11	1	NM_001282547.2	A1	Q8N2I9-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000678

AC:

AN:

250664

Hom.:

AF XY:

0.0000959

AC XY:

AN XY:

135554

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000897

AC:

130

AN:

1449752

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

718594

show subpopulations

Gnomad4 AFR exome

AF:

0.000661

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000826

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.000184

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000166

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.00115

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.305C>T (p.T102M) 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 305, causing the threonine (T) at amino acid position 102 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.32

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Benign

0.064

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;.;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.59

N;N;.;N

MutationTaster

Benign

0.77

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

0.47

P;P;P;P

Vest4

0.41

MVP

0.26

MPC

0.77

ClinPred

0.10

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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