chr20-44975362-C-T

Variant names:

• chr20-44975362-C-T
• rs6017452
• NM_006282.5:c.117-3081C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006282.5(STK4):​c.117-3081C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 980,010 control chromosomes in the GnomAD database, including 117,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (22329 hom., cov: 32)
  • Exomes 𝑓: 0.48 (95158 hom.)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.751

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 20-44975362-C-T is Benign according to our data. Variant chr20-44975362-C-T is described in ClinVar as [Benign]. Clinvar id is 2688087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5	c.117-3081C>T		intron_variant	Intron 2 of 10	ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.117-3081C>T		intron_variant	Intron 2 of 10	1	NM_006282.5	ENSP00000361892.3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80332 AN: 151906 Hom.: 22287 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.477 AC: 394578 AN: 827984 Hom.: 95158 Cov.: 29 AF XY: 0.476 AC XY: 182243 AN XY: 382520

Gnomad4 AFR exome AF: 0.690

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.529 AC: 80429 AN: 152026 Hom.: 22329 Cov.: 32 AF XY: 0.528 AC XY: 39216 AN XY: 74300

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.529

Alfa AF: 0.488 Hom.: 9509

Bravo AF: 0.516

Asia WGS AF: 0.419 AC: 1463 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: 53. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.9
DANN	Benign	0.40

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: rs6017452; hg19: chr20-43604003;