X-132073051-T-C

Position:

• chrX-132073051-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016542.4(STK26):​c.1184T>C​(p.Ile395Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: STK26 NM_016542.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

Genes affected

STK26 (HGNC:18174): (serine/threonine kinase 26) The product of this gene is a member of the GCK group III family of kinases, which are a subset of the Ste20-like kinases. The encoded protein contains an amino-terminal kinase domain, and a carboxy-terminal regulatory domain that mediates homodimerization. The protein kinase localizes to the Golgi apparatus and is specifically activated by binding to the Golgi matrix protein GM130. It is also cleaved by caspase-3 in vitro, and may function in the apoptotic pathway. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30922997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK26	NM_016542.4	c.1184T>C	p.Ile395Thr	missense_variant	11/12	ENST00000394334.7	NP_057626.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK26	ENST00000394334.7	c.1184T>C	p.Ile395Thr	missense_variant	11/12	1	NM_016542.4	ENSP00000377867.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.1184T>C (p.I395T) alteration is located in exon 11 (coding exon 10) of the STK26 gene. This alteration results from a T to C substitution at nucleotide position 1184, causing the isoleucine (I) at amino acid position 395 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;T;.;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T;T;D;T;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.91	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D;D;T;D;D
Sift4G	Benign	0.089	T;T;T;T;T
Polyphen		0.25	B;B;B;B;P
Vest4		0.70
MutPred		0.41		.;Loss of stability (P = 0.0339);.;.;.;
MVP		0.66
MPC		0.97
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.67
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-131207079;