rs7104660

Variant names:

• chr11-125606751-G-A
• rs7104660
• NM_152713.5:c.780+286G>A

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.780+286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0491 in 152,238 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.049 (209 hom., cov: 32)
• Consequence: STT3A NM_152713.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.146
• Publications: 1 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: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• STT3A-congenital disorder of glycosylation

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-125606751-G-A is Benign according to our data. Variant chr11-125606751-G-A is described in ClinVar as Benign. ClinVar VariationId is 1258622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0542 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3A	NM_152713.5	MANE Select	c.780+286G>A		intron	N/A	NP_689926.1
	STT3A	NM_001278503.2		c.780+286G>A		intron	N/A	NP_001265432.1
	STT3A	NM_001278504.2		c.504+286G>A		intron	N/A	NP_001265433.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3A	ENST00000392708.9	TSL:1 MANE Select	c.780+286G>A		intron	N/A	ENSP00000376472.3
	STT3A	ENST00000529196.5	TSL:1	c.780+286G>A		intron	N/A	ENSP00000436962.1
	STT3A	ENST00000534472.5	TSL:1	n.915+286G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7467 AN: 152120 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0390

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.0295

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0491 AC: 7481 AN: 152238 Hom.: 209 Cov.: 32 AF XY: 0.0474 AC XY: 3529 AN XY: 74422

African (AFR) AF: 0.0490 AC: 2037 AN: 41542

American (AMR) AF: 0.0389 AC: 595 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4822

European-Finnish (FIN) AF: 0.0295 AC: 313 AN: 10600

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0557 AC: 3790 AN: 68016

Other (OTH) AF: 0.0644 AC: 136 AN: 2112

Alfa AF: 0.0494 Hom.: 82

Bravo AF: 0.0505

Asia WGS AF: 0.0310 AC: 106 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
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.32
PhyloP100		0.15
PromoterAI		-0.0064	Neutral
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: rs7104660; hg19: chr11-125476646;