rs866141679

Variant names:

• chr11-125592935-A-G
• rs866141679
• NM_152713.5:c.-36+17A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152713.5(STT3A):​c.-36+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00053 in 169,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: STT3A NM_152713.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-125592935-A-G is Benign according to our data. Variant chr11-125592935-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 387269.Status of the report is criteria_provided_single_submitter, 1 stars.

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+17A>G		intron	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.-124+17A>G		intron	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-189+17A>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.-36+17A>G		intron	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.-124+17A>G		intron	N/A	ENSP00000436962.1	P46977-1
	STT3A	ENST00000534472.5	TSL:1	n.100+17A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 88 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.000112 AC: 2 AN: 17856 Hom.: 0 Cov.: 0 AF XY: 0.0000978 AC XY: 1 AN XY: 10224

African (AFR) AF: 0.00 AC: 0 AN: 292

American (AMR) AF: 0.00 AC: 0 AN: 1390

Ashkenazi Jewish (ASJ) AF: 0.00901 AC: 2 AN: 222

East Asian (EAS) AF: 0.00 AC: 0 AN: 620

South Asian (SAS) AF: 0.00 AC: 0 AN: 4462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 30

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 9526

Other (OTH) AF: 0.00 AC: 0 AN: 698

GnomAD4 genome AF: 0.000579 AC: 88 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.000673 AC XY: 50 AN XY: 74298

African (AFR) AF: 0.000217 AC: 9 AN: 41438

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68022

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.000741 Hom.: 0

Bravo AF: 0.000665

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.58
DANN	Benign	0.42
PhyloP100		-1.6
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs866141679; hg19: chr11-125462830;