chr20-44995017-C-T

Variant names:

• chr20-44995017-C-T
• rs6017460
• NM_006282.5:c.526-73C>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.526-73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,059,060 control chromosomes in the GnomAD database, including 119,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (14309 hom., cov: 27)
  • Exomes 𝑓: 0.48 (104926 hom.)
• Consequence: STK4 NM_006282.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17

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=-0.96).
• BP6: Variant 20-44995017-C-T is Benign according to our data. Variant chr20-44995017-C-T is described in ClinVar as [Benign]. Clinvar id is 2628218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5	c.526-73C>T		intron_variant	Intron 5 of 10	ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.526-73C>T		intron_variant	Intron 5 of 10	1	NM_006282.5	ENSP00000361892.3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 63841 AN: 144886 Hom.: 14290 Cov.: 27

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.484 AC: 442028 AN: 914080 Hom.: 104926 AF XY: 0.484 AC XY: 216066 AN XY: 445958

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.441 AC: 63891 AN: 144980 Hom.: 14309 Cov.: 27 AF XY: 0.442 AC XY: 31167 AN XY: 70510

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.463

Alfa AF: 0.345 Hom.: 1283

Bravo AF: 0.404

Asia WGS AF: 0.348 AC: 1206 AN: 3454

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

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 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 36. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.45
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: rs6017460; hg19: chr20-43623658; COSMIC: COSV65670720;