20-44975362-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.99).
• BP6: Variant 20-44975362-C-T is Benign according to our data. Variant chr20-44975362-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006282.5. 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.117-3081C>T		intron	N/A	NP_006273.1
	STK4	NM_001352385.2		c.117-3081C>T		intron	N/A	NP_001339314.1
	STK4	NR_147974.2		n.1569C>T		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK4	ENST00000372806.8	TSL:1 MANE Select	c.117-3081C>T		intron	N/A	ENSP00000361892.3
	STK4	ENST00000499879.8	TSL:1	c.117-3081C>T		intron	N/A	ENSP00000443514.1
	STK4	ENST00000488618.2	TSL:1	n.2710C>T		non_coding_transcript_exon	Exon 3 of 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

African (AFR) AF: 0.690 AC: 10808 AN: 15674

American (AMR) AF: 0.334 AC: 327 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 2599 AN: 5118

East Asian (EAS) AF: 0.340 AC: 1227 AN: 3604

South Asian (SAS) AF: 0.384 AC: 6281 AN: 16358

European-Finnish (FIN) AF: 0.607 AC: 165 AN: 272

Middle Eastern (MID) AF: 0.473 AC: 763 AN: 1614

European-Non Finnish (NFE) AF: 0.475 AC: 359597 AN: 757230

Other (OTH) AF: 0.472 AC: 12811 AN: 27134

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

African (AFR) AF: 0.682 AC: 28266 AN: 41460

American (AMR) AF: 0.369 AC: 5643 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1751 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1763 AN: 5170

South Asian (SAS) AF: 0.388 AC: 1870 AN: 4816

European-Finnish (FIN) AF: 0.601 AC: 6342 AN: 10560

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33057 AN: 67950

Other (OTH) AF: 0.529 AC: 1120 AN: 2116

Alfa AF: 0.488 Hom.: 10415

Bravo AF: 0.516

Asia WGS AF: 0.419 AC: 1463 AN: 3478

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	-0.99
CADD	Benign	3.9
DANN	Benign	0.40
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs6017452; hg19: chr20-43604003;