rs368513990

Variant names:

• chr20-44981942-C-G
• NM_006282.5:c.359C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-44981942-C-G
• chr20-44981942-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006282.5(STK4):​c.359C>G​(p.Thr120Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STK4 NM_006282.5 missense, splice_region
• Scores: Splicing: ADA: 0.9771
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.47

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK4	NM_006282.5	c.359C>G	p.Thr120Arg	missense_variant, splice_region_variant	Exon 4 of 11	ENST00000372806.8	NP_006273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK4	ENST00000372806.8	c.359C>G	p.Thr120Arg	missense_variant, splice_region_variant	Exon 4 of 11	1	NM_006282.5	ENSP00000361892.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455164 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724500

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.;.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	-0.075	N;.;N;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.1	D;D;D;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0020	D;D;T;.
Sift4G	Uncertain	0.060	T;D;T;T
Polyphen		0.72	P;D;P;.
Vest4		0.76
MutPred		0.49		Gain of methylation at K119 (P = 0.0464);Gain of methylation at K119 (P = 0.0464);Gain of methylation at K119 (P = 0.0464);.;
MVP		0.69
MPC		0.41
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.90
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.85
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-43610583;