rs375341793

Variant names:

• chr8-52113315-A-C
• rs375341793
• NM_001352837.2:c.3027T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-52113315-A-C
• chr8-52113315-A-T

Variant summary

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

The NM_001352837.2(ST18):​c.3027T>G​(p.Phe1009Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ST18 NM_001352837.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• 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.3027T>G	p.Phe1009Leu	missense_variant	Exon 26 of 26	ENST00000689386.1	NP_001339766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST18	ENST00000689386.1	c.3027T>G	p.Phe1009Leu	missense_variant	Exon 26 of 26		NM_001352837.2	ENSP00000509475.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461626 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727104

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111864

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.36
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.029	D
Sift4G	Benign	0.082	T
Polyphen		1.0	D
Vest4		0.68
MutPred		0.47		Gain of disorder (P = 0.1088);
MVP		0.42
MPC		0.52
ClinPred		1.0	D
GERP RS		-1.3
Varity_R		0.53
gMVP		0.77
Mutation Taster		=62/38	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

dbSNP: rs375341793; hg19: chr8-53025875;