20-44972032-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006282.5(STK4):c.36-46C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,547,962 control chromosomes in the GnomAD database, including 175,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20040 hom., cov: 32)
  • Exomes 𝑓: 0.47 (155764 hom.)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.304

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-44972032-C-G is Benign according to our data. Variant chr20-44972032-C-G is described in ClinVar as [Benign]. Clinvar id is 1334913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK4	NM_006282.5	c.36-46C>G		intron_variant		ENST00000372806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK4	ENST00000372806.8	c.36-46C>G		intron_variant		1	NM_006282.5	P1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76441 AN: 151852 Hom.: 20003 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.504

GnomAD3 exomes AF: 0.443 AC: 109470 AN: 247332 Hom.: 26051 AF XY: 0.447 AC XY: 59937 AN XY: 134108

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.228

Gnomad SAS exome AF: 0.394

Gnomad FIN exome AF: 0.574

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.462

GnomAD4 exome AF: 0.466 AC: 650967 AN: 1395992 Hom.: 155764 Cov.: 21 AF XY: 0.465 AC XY: 325057 AN XY: 698330

Gnomad4 AFR exome AF: 0.605

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.504 AC: 76529 AN: 151970 Hom.: 20040 Cov.: 32 AF XY: 0.502 AC XY: 37272 AN XY: 74264

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.506

Alfa AF: 0.495 Hom.: 3362

Bravo AF: 0.490

Asia WGS AF: 0.357 AC: 1247 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 56% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. Only high quality variants are reported. -

Combined immunodeficiency due to STK4 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.58

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

LitVar

Other links and lift over

dbSNP: rs6130717; hg19: chr20-43600673; COSMIC: COSV65670077;