rs2298483

Positions:

• chr11-125625127-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000526364.1(STT3A):​n.529C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 221,698 control chromosomes in the GnomAD database, including 2,595 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1767 hom., cov: 32)
  • Exomes 𝑓: 0.15 (828 hom.)
• Consequence: STT3A ENST00000526364.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672

Genes affected

STT3A (HGNC:6172): (STT3 oligosaccharyltransferase complex catalytic subunit A) The protein encoded by this gene is a catalytic subunit of the N-oligosaccharyltransferase (OST) complex, which functions in the endoplasmic reticulum to transfer glycan chains to asparagine residues of target proteins. A separate complex containing a similar catalytic subunit with an overlapping function also exists. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

CHEK1 (HGNC:1925): (checkpoint kinase 1) The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHEK1	NM_001114122.3			upstream_gene_variant		ENST00000438015.7	NP_001107594.1
LOC118567325	NR_170378.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STT3A	ENST00000526364.1	n.529C>T		non_coding_transcript_exon_variant	4/4	3
CHEK1	ENST00000438015.7			upstream_gene_variant		5	NM_001114122.3	ENSP00000388648	P1
	ENST00000686400.2			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19665 AN: 152096 Hom.: 1763 Cov.: 32

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.147 AC: 10230 AN: 69484 Hom.: 828 Cov.: 0 AF XY: 0.149 AC XY: 4778 AN XY: 32074

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.0926

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.129 AC: 19662 AN: 152214 Hom.: 1767 Cov.: 32 AF XY: 0.131 AC XY: 9740 AN XY: 74376

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.144

Alfa AF: 0.147 Hom.: 2686

Bravo AF: 0.139

Asia WGS AF: 0.171 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2298483; hg19: chr11-125495022;