20-44973280-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3 BP6_Moderate BA1

The NM_006282.5(STK4):c.116+1122G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,926 control chromosomes in the GnomAD database, including 22,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (22180 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.221

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 -9 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 20-44973280-G-T is Benign according to our data. Variant chr20-44973280-G-T is described in ClinVar as [Benign]. Clinvar id is 2688413.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK4	NM_006282.5	c.116+1122G>T		intron_variant		ENST00000372806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK4	ENST00000372806.8	c.116+1122G>T		intron_variant		1	NM_006282.5	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80048 AN: 151808 Hom.: 22138 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.524

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.528 AC: 80145 AN: 151926 Hom.: 22180 Cov.: 32 AF XY: 0.526 AC XY: 39076 AN XY: 74232

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.528

Alfa AF: 0.426 Hom.: 1780

Bravo AF: 0.515

Asia WGS AF: 0.412 AC: 1438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Uncertain	23
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.52		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.52		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs910671; hg19: chr20-43601921;