rs772676191

Variant names:

• chr13-98466384-G-C
• rs772676191
• NM_001032296.4:c.775C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001032296.4(STK24):​c.775C>G​(p.Pro259Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,459,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: STK24 NM_001032296.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.94
• Publications: 1 publications found

Genes affected

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032296.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK24	NM_001032296.4	MANE Select	c.775C>G	p.Pro259Ala	missense	Exon 6 of 11	NP_001027467.2	Q9Y6E0-2
	STK24	NM_003576.5		c.811C>G	p.Pro271Ala	missense	Exon 6 of 11	NP_003567.2
	STK24	NM_001286649.2		c.718C>G	p.Pro240Ala	missense	Exon 5 of 10	NP_001273578.1	B4DR80

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK24	ENST00000539966.6	TSL:1 MANE Select	c.775C>G	p.Pro259Ala	missense	Exon 6 of 11	ENSP00000442539.2	Q9Y6E0-2
	STK24	ENST00000376547.7	TSL:1	c.811C>G	p.Pro271Ala	missense	Exon 6 of 11	ENSP00000365730.3	Q9Y6E0-1
	STK24	ENST00000444574.1	TSL:1	c.526C>G	p.Pro176Ala	missense	Exon 5 of 10	ENSP00000402764.1	H0Y630

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251098 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1459864 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726238

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111920

Other (OTH) AF: 0.0000166 AC: 1 AN: 60208

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Uncertain	0.50
Sift	Benign	0.043	D
Sift4G	Uncertain	0.037	D
Polyphen		0.50	P
Vest4		0.26
MutPred		0.79		Loss of disorder (P = 0.0632)
MVP		0.71
MPC		1.1
ClinPred		0.48	T
GERP RS		5.2
PromoterAI		-0.0079	Neutral
Varity_R		0.74
gMVP		0.69
Mutation Taster		=8/92	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs772676191; hg19: chr13-99118638;