Genetic Variant STK40:p.Ala146Ala (chr1-36355338-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001282547.2(STK40):c.438T>C(p.Ala146Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,614,178 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 7 hom. )

Consequence

STK40
NM_001282547.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.29

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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-36355338-A-G is Benign according to our data. Variant chr1-36355338-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638671.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.29 with no splicing effect.

BS2

High AC in GnomAd4 at 359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK40	NM_001282547.2 link	c.438T>C	p.Ala146Ala	synonymous_variant	Exon 5 of 11	ENST00000373132.4	NP_001269476.1	Q8N2I9-1
STK40	NM_001282546.2 link	c.453T>C	p.Ala151Ala	synonymous_variant	Exon 5 of 11		NP_001269475.1	Q8N2I9-4
STK40	NM_032017.3 link	c.438T>C	p.Ala146Ala	synonymous_variant	Exon 6 of 12		NP_114406.1	Q8N2I9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK40	ENST00000373132.4 link	c.438T>C	p.Ala146Ala	synonymous_variant	Exon 5 of 11	1	NM_001282547.2	ENSP00000362224.4		Q8N2I9-1

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00230

AC:

578

AN:

251488

AF XY:

0.00236

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00993

Gnomad NFE exome

AF:

0.00224

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00250

AC:

3656

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1748

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33478

American (AMR)

AF:

0.00116

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00198

AC:

171

AN:

86258

European-Finnish (FIN)

AF:

0.00985

AC:

526

AN:

53420

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00248

AC:

2755

AN:

1112010

Other (OTH)

AF:

0.00219

AC:

132

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

240

481

721

962

1202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00236

AC:

359

AN:

152292

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41568

American (AMR)

AF:

0.00163

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0115

AC:

122

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00273

AC:

186

AN:

68018

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00207

Hom.:

Bravo

AF:

0.00153

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

STK40: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.16

(source)

DANN

Benign

0.46

PhyloP100

-2.3

Mutation Taster

=97/3

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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1-36355338-A-G

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