8-52132117-G-A

Variant names:

• chr8-52132117-G-A
• NM_001352837.2:c.2507C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001352837.2(ST18):​c.2507C>T​(p.Thr836Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST18 NM_001352837.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02
• Publications: 0 publications found

Genes affected

ST18 (HGNC:18695): (ST18 C2H2C-type zinc finger transcription factor) Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cytokine-mediated signaling pathway; negative regulation of cell population proliferation; and positive regulation of nitrogen compound metabolic process. Located in nucleus. Part of protein-DNA complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST18	NM_001352837.2	c.2507C>T	p.Thr836Ile	missense_variant	Exon 22 of 26	ENST00000689386.1	NP_001339766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST18	ENST00000689386.1	c.2507C>T	p.Thr836Ile	missense_variant	Exon 22 of 26		NM_001352837.2	ENSP00000509475.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2507C>T (p.T836I) alteration is located in exon 22 (coding exon 16) of the ST18 gene. This alteration results from a C to T substitution at nucleotide position 2507, causing the threonine (T) at amino acid position 836 to be replaced by an isoleucine (I). 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	0.69
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.56		Loss of phosphorylation at T836 (P = 0.0484);
MVP		0.068
MPC		0.46
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.49
gMVP		0.69
Mutation Taster		=53/47	polymorphism

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

hg19: chr8-53044677;