8-52133288-C-T

Position:

• chr8-52133288-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001352837.2(ST18):​c.2314G>A​(p.Gly772Ser) 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 pathogenic outcome for this variant. 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: 7.88

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST18	NM_001352837.2	c.2314G>A	p.Gly772Ser	missense_variant	20/26	ENST00000689386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST18	ENST00000689386.1	c.2314G>A	p.Gly772Ser	missense_variant	20/26		NM_001352837.2	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.2314G>A (p.G772S) alteration is located in exon 20 (coding exon 14) of the ST18 gene. This alteration results from a G to A substitution at nucleotide position 2314, causing the glycine (G) at amino acid position 772 to be replaced by a serine (S). 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	0.23
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.97
MutPred		0.84		Gain of phosphorylation at G772 (P = 0.0723);
MVP		0.54
MPC		0.42
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.65
gMVP		0.62

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: chr8-53045848;