rs12289190

Variant names:

• chr11-125596106-A-G
• rs12289190
• NM_152713.5:c.88+103A>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+103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 890,458 control chromosomes in the GnomAD database, including 2,774 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: 0.057 (1555 hom.)
• Consequence: STT3A NM_152713.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271
• 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: 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=-0.83).
• BP6: Variant 11-125596106-A-G is Benign according to our data. Variant chr11-125596106-A-G is described in ClinVar as Benign. ClinVar VariationId is 1292105.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+103A>G		intron	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.88+103A>G		intron	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-188-953A>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+103A>G		intron	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.88+103A>G		intron	N/A	ENSP00000436962.1	P46977-1
	STT3A	ENST00000534472.5	TSL:1	n.223+103A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16172 AN: 152054 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.0566 AC: 41752 AN: 738286 Hom.: 1555 AF XY: 0.0557 AC XY: 21531 AN XY: 386350

African (AFR) AF: 0.206 AC: 3481 AN: 16932

American (AMR) AF: 0.0466 AC: 1268 AN: 27226

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 1273 AN: 17394

East Asian (EAS) AF: 0.0172 AC: 610 AN: 35460

South Asian (SAS) AF: 0.0438 AC: 2605 AN: 59532

European-Finnish (FIN) AF: 0.0476 AC: 2241 AN: 47122

Middle Eastern (MID) AF: 0.115 AC: 451 AN: 3924

European-Non Finnish (NFE) AF: 0.0551 AC: 27275 AN: 494854

Other (OTH) AF: 0.0711 AC: 2548 AN: 35842

GnomAD4 genome AF: 0.106 AC: 16202 AN: 152172 Hom.: 1219 Cov.: 32 AF XY: 0.103 AC XY: 7693 AN XY: 74426

African (AFR) AF: 0.218 AC: 9056 AN: 41450

American (AMR) AF: 0.0648 AC: 991 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

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

South Asian (SAS) AF: 0.0551 AC: 266 AN: 4826

European-Finnish (FIN) AF: 0.0437 AC: 464 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0673 AC: 4574 AN: 68008

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 as Germline

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	-0.83
CADD	Benign	8.6
DANN	Benign	0.80
PhyloP100		-0.27
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: rs12289190; hg19: chr11-125466001;