11-125593855-GTGTTGT-GTGT

Variant names:

• chr11-125593855-GTGT-G
• rs10538228
• NM_152713.5:c.-36+948_-36+950delGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_152713.5(STT3A):​c.-36+948_-36+950delGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17213 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STT3A NM_152713.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.906
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 11-125593855-GTGT-G is Benign according to our data. Variant chr11-125593855-GTGT-G is described in ClinVar as Benign. ClinVar VariationId is 1292244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.58 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.-36+948_-36+950delGTT		intron	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.-36+141_-36+143delGTT		intron	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-189+948_-189+950delGTT		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.-36+938_-36+940delTGT		intron	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.-36+131_-36+133delTGT		intron	N/A	ENSP00000436962.1	P46977-1
	STT3A	ENST00000534472.5	TSL:1	n.100+938_100+940delTGT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69441 AN: 151560 Hom.: 17207 Cov.: 0

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.474

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.458 AC: 69456 AN: 151678 Hom.: 17213 Cov.: 0 AF XY: 0.457 AC XY: 33884 AN XY: 74092

African (AFR) AF: 0.243 AC: 10064 AN: 41424

American (AMR) AF: 0.572 AC: 8697 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1813 AN: 3456

East Asian (EAS) AF: 0.517 AC: 2661 AN: 5148

South Asian (SAS) AF: 0.598 AC: 2880 AN: 4816

European-Finnish (FIN) AF: 0.438 AC: 4601 AN: 10498

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37175 AN: 67814

Other (OTH) AF: 0.476 AC: 1003 AN: 2108

Alfa AF: 0.375 Hom.: 1103

Bravo AF: 0.457

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

ClinVar submissions as Germline

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
PhyloP100		0.91
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: rs10538228; hg19: chr11-125463750;