20-44995017-C-T

Variant names:

• chr20-44995017-C-T
• rs6017460
• NM_006282.5:c.526-73C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000372806.8(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 ENST00000372806.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to STK4 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372806.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	NM_006282.5	MANE Select	c.526-73C>T		intron	N/A	NP_006273.1
	STK4	NM_001352385.2		c.526-73C>T		intron	N/A	NP_001339314.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	ENST00000372806.8	TSL:1 MANE Select	c.526-73C>T		intron	N/A	ENSP00000361892.3
	STK4	ENST00000499879.8	TSL:1	c.361-73C>T		intron	N/A	ENSP00000443514.1
	STK4	ENST00000372801.5	TSL:2	c.526-73C>T		intron	N/A	ENSP00000361887.1

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

African (AFR) AF: 0.381 AC: 7258 AN: 19066

American (AMR) AF: 0.274 AC: 4376 AN: 15954

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 7158 AN: 13378

East Asian (EAS) AF: 0.225 AC: 5494 AN: 24456

South Asian (SAS) AF: 0.397 AC: 10027 AN: 25266

European-Finnish (FIN) AF: 0.600 AC: 21091 AN: 35174

Middle Eastern (MID) AF: 0.474 AC: 1745 AN: 3678

European-Non Finnish (NFE) AF: 0.496 AC: 367188 AN: 740266

Other (OTH) AF: 0.480 AC: 17691 AN: 36842

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

African (AFR) AF: 0.370 AC: 14383 AN: 38882

American (AMR) AF: 0.342 AC: 4898 AN: 14316

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1724 AN: 3430

East Asian (EAS) AF: 0.253 AC: 1208 AN: 4766

South Asian (SAS) AF: 0.396 AC: 1802 AN: 4552

European-Finnish (FIN) AF: 0.603 AC: 5649 AN: 9368

Middle Eastern (MID) AF: 0.549 AC: 157 AN: 286

European-Non Finnish (NFE) AF: 0.492 AC: 32689 AN: 66496

Other (OTH) AF: 0.463 AC: 931 AN: 2012

Alfa AF: 0.345 Hom.: 1283

Bravo AF: 0.404

Asia WGS AF: 0.348 AC: 1206 AN: 3454

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.45
DANN	Benign	0.40
PhyloP100		-2.2
Mutation Taster		=11/89	disease causing (long InDel)

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

Other links and lift over

dbSNP: rs6017460; hg19: chr20-43623658; COSMIC: COSV65670720;