11-125596115-T-G

Variant names:

• chr11-125596115-T-G
• rs10082634
• NM_152713.5:c.88+112T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152713.5(STT3A):​c.88+112T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 837,196 control chromosomes in the GnomAD database, including 2,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1219 hom., cov: 32)
  • Exomes 𝑓: 0.058 (1481 hom.)
• Consequence: STT3A NM_152713.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.762
• Publications: 3 publications found

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]

STT3A Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type Iw, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia
• STT3A-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-125596115-T-G is Benign according to our data. Variant chr11-125596115-T-G is described in ClinVar as Benign. ClinVar VariationId is 1244774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152713.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3A	NM_152713.5	MANE Select	c.88+112T>G		intron	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.88+112T>G		intron	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-188-944T>G		intron	N/A	NP_001265433.1	P46977-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3A	ENST00000392708.9	TSL:1 MANE Select	c.88+112T>G		intron	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.88+112T>G		intron	N/A	ENSP00000436962.1	P46977-1
	STT3A	ENST00000534472.5	TSL:1	n.223+112T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16172 AN: 152050 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0783

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.0552

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.0583 AC: 39927 AN: 685028 Hom.: 1481 AF XY: 0.0569 AC XY: 20466 AN XY: 359372

African (AFR) AF: 0.209 AC: 3370 AN: 16160

American (AMR) AF: 0.0457 AC: 1191 AN: 26034

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 1219 AN: 16586

East Asian (EAS) AF: 0.0172 AC: 600 AN: 34942

South Asian (SAS) AF: 0.0435 AC: 2455 AN: 56424

European-Finnish (FIN) AF: 0.0468 AC: 2126 AN: 45382

Middle Eastern (MID) AF: 0.114 AC: 420 AN: 3690

European-Non Finnish (NFE) AF: 0.0577 AC: 26083 AN: 451786

Other (OTH) AF: 0.0724 AC: 2463 AN: 34024

GnomAD4 genome AF: 0.106 AC: 16202 AN: 152168 Hom.: 1219 Cov.: 32 AF XY: 0.103 AC XY: 7691 AN XY: 74422

African (AFR) AF: 0.219 AC: 9055 AN: 41432

American (AMR) AF: 0.0647 AC: 991 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0783 AC: 272 AN: 3472

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5190

South Asian (SAS) AF: 0.0551 AC: 266 AN: 4830

European-Finnish (FIN) AF: 0.0438 AC: 464 AN: 10602

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4575 AN: 68016

Other (OTH) AF: 0.106 AC: 225 AN: 2116

Alfa AF: 0.0901 Hom.: 105

Bravo AF: 0.114

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10082634; hg19: chr11-125466010;