11-125596010-G-T

Variant names:

• chr11-125596010-G-T
• rs79017058
• NM_152713.5:c.88+7G>T

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+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 1,595,324 control chromosomes in the GnomAD database, including 3,474 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (409 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3065 hom.)
• Consequence: STT3A NM_152713.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001904
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0150
• Publications: 4 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• STT3A-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, G2P, Orphanet, Ambry Genetics, 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 11-125596010-G-T is Benign according to our data. Variant chr11-125596010-G-T is described in ClinVar as Benign. ClinVar VariationId is 380013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0948 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+7G>T		splice_region intron	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.88+7G>T		splice_region intron	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-188-1049G>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.88+7G>T		splice_region intron	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.88+7G>T		splice_region intron	N/A	ENSP00000436962.1	P46977-1
	STT3A	ENST00000534472.5	TSL:1	n.223+7G>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10680 AN: 152132 Hom.: 408 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0832

GnomAD2 exomes AF: 0.0560 AC: 13691 AN: 244632 AF XY: 0.0554

Gnomad AFR exome AF: 0.0978

Gnomad AMR exome AF: 0.0361

Gnomad ASJ exome AF: 0.0756

Gnomad EAS exome AF: 0.000664

Gnomad FIN exome AF: 0.0458

Gnomad NFE exome AF: 0.0687

Gnomad OTH exome AF: 0.0701

GnomAD4 exome AF: 0.0612 AC: 88317 AN: 1443074 Hom.: 3065 Cov.: 27 AF XY: 0.0602 AC XY: 43243 AN XY: 718328

African (AFR) AF: 0.101 AC: 3283 AN: 32628

American (AMR) AF: 0.0387 AC: 1682 AN: 43480

Ashkenazi Jewish (ASJ) AF: 0.0751 AC: 1946 AN: 25896

East Asian (EAS) AF: 0.000457 AC: 18 AN: 39426

South Asian (SAS) AF: 0.0379 AC: 3192 AN: 84272

European-Finnish (FIN) AF: 0.0484 AC: 2583 AN: 53344

Middle Eastern (MID) AF: 0.104 AC: 597 AN: 5720

European-Non Finnish (NFE) AF: 0.0647 AC: 71108 AN: 1098574

Other (OTH) AF: 0.0654 AC: 3908 AN: 59734

GnomAD4 genome AF: 0.0702 AC: 10692 AN: 152250 Hom.: 409 Cov.: 32 AF XY: 0.0680 AC XY: 5063 AN XY: 74452

African (AFR) AF: 0.0973 AC: 4038 AN: 41518

American (AMR) AF: 0.0495 AC: 757 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5196

South Asian (SAS) AF: 0.0409 AC: 197 AN: 4822

European-Finnish (FIN) AF: 0.0437 AC: 463 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0667 AC: 4540 AN: 68022

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

Alfa AF: 0.0706 Hom.: 220

Bravo AF: 0.0727

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.74
PhyloP100		-0.015
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.012
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: rs79017058; hg19: chr11-125465905;