Genetic Variant ST18:p.Gln973Arg (chr8-52116360-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001352837.2(ST18):c.2918A>G(p.Gln973Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,722 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ST18
NM_001352837.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

Publications

0 publications found

Variant links:

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]

ST18 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST18	NM_001352837.2 link	c.2918A>G	p.Gln973Arg	missense_variant	Exon 25 of 26	ENST00000689386.1	NP_001339766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST18	ENST00000689386.1 link	c.2918A>G	p.Gln973Arg	missense_variant	Exon 25 of 26		NM_001352837.2	ENSP00000509475.1		O60284

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111924

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2918A>G (p.Q973R) alteration is located in exon 25 (coding exon 19) of the ST18 gene. This alteration results from a A to G substitution at nucleotide position 2918, causing the glutamine (Q) at amino acid position 973 to be replaced by an arginine (R). 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

Benign

0.15

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.0

PhyloP100

6.2

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.16

Sift

Uncertain

0.0050

Sift4G

Benign

0.077

Polyphen

1.0

Vest4

0.79

MutPred

0.15

Gain of helix (P = 0.0496);

MVP

0.28

MPC

0.34

ClinPred

0.99

GERP RS

5.6

Varity_R

0.62

gMVP

0.58

Mutation Taster

=80/20

polymorphism

(source)

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

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8-52116360-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over