Variant 20-44995083-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006282.5(STK4):c.526-7A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,572,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

STK4
NM_006282.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004434

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.74

Variant links:

Genes affected

STK4 (HGNC:11408): (serine/threonine kinase 4) The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process. [provided by RefSeq, Jul 2008]

STK4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-44995083-A-G is Benign according to our data. Variant chr20-44995083-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 473299.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK4	NM_006282.5 linkuse as main transcript	c.526-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000372806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK4	ENST00000372806.8 linkuse as main transcript	c.526-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006282.5	P1	Q13043-1

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

143850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000775

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000563

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000348

Gnomad OTH

AF:

0.000520

GnomAD3 exomes

AF:

0.000280

AC:

AN:

235660

Hom.:

AF XY:

0.000266

AC XY:

AN XY:

127768

show subpopulations

Gnomad AFR exome

AF:

0.0000671

Gnomad AMR exome

AF:

0.000384

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000655

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

AF:

0.000228

AC:

326

AN:

1429020

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

167

AN XY:

710482

show subpopulations

Gnomad4 AFR exome

AF:

0.0000622

Gnomad4 AMR exome

AF:

0.000331

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000535

Gnomad4 NFE exome

AF:

0.000250

Gnomad4 OTH exome

AF:

0.0000850

GnomAD4 genome

AF:

0.000264

AC:

AN:

143850

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

AN XY:

69408

show subpopulations

Gnomad4 AFR

AF:

0.0000775

Gnomad4 AMR

AF:

0.000425

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000563

Gnomad4 NFE

AF:

0.000348

Gnomad4 OTH

AF:

0.000520

Alfa

AF:

0.000204

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Combined immunodeficiency due to STK4 deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 03, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.19

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.0020

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

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