11-125596781-G-T

Variant names:

• chr11-125596781-G-T
• rs78574330
• NM_152713.5:c.89-278G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152713.5(STT3A):​c.89-278G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 152,176 control chromosomes in the GnomAD database, including 516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.077 (516 hom., cov: 32)
• Consequence: STT3A NM_152713.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.304
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-125596781-G-T is Benign according to our data. Variant chr11-125596781-G-T is described in ClinVar as Benign. ClinVar VariationId is 1244349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 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.89-278G>T		intron	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.89-278G>T		intron	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-188-278G>T		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.89-278G>T		intron	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.89-278G>T		intron	N/A	ENSP00000436962.1	P46977-1
	STT3A	ENST00000534472.5	TSL:1	n.224-278G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0770 AC: 11701 AN: 152058 Hom.: 515 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0508

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0770 AC: 11717 AN: 152176 Hom.: 516 Cov.: 32 AF XY: 0.0747 AC XY: 5556 AN XY: 74408

African (AFR) AF: 0.120 AC: 4976 AN: 41488

American (AMR) AF: 0.0517 AC: 790 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 270 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.0510 AC: 246 AN: 4822

European-Finnish (FIN) AF: 0.0436 AC: 462 AN: 10592

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0667 AC: 4540 AN: 68016

Other (OTH) AF: 0.0861 AC: 182 AN: 2114

Alfa AF: 0.0524 Hom.: 89

Bravo AF: 0.0798

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.30
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: rs78574330; hg19: chr11-125466676;