chr8-52142990-G-T

Position:

• chr8-52142990-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001352837.2(ST18):​c.2108C>A​(p.Ala703Asp) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: ST18 NM_001352837.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23221117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST18	NM_001352837.2	c.2108C>A	p.Ala703Asp	missense_variant	17/26	ENST00000689386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST18	ENST00000689386.1	c.2108C>A	p.Ala703Asp	missense_variant	17/26		NM_001352837.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 20, 2021

The c.2108C>A (p.A703D) alteration is located in exon 17 (coding exon 11) of the ST18 gene. This alteration results from a C to A substitution at nucleotide position 2108, causing the alanine (A) at amino acid position 703 to be replaced by an aspartic acid (D). 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	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	0.83	N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.046
Sift	Benign	0.040	D
Sift4G	Benign	0.062	T
Polyphen		0.73	P
Vest4		0.37
MutPred		0.43		Gain of relative solvent accessibility (P = 0.1571);
MVP		0.082
MPC		0.27
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.32
gMVP		0.45

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: chr8-53055550;