NM_152713.5:c.-35-124C>T

Variant names:

• chr11-125595757-C-T
• rs10082593
• NM_152713.5:c.-35-124C>T

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.-35-124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00907 in 608,318 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (125 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (45 hom.)
• Consequence: STT3A NM_152713.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 11-125595757-C-T is Benign according to our data. Variant chr11-125595757-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 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.-35-124C>T		intron	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.-35-124C>T		intron	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-188-1302C>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.-35-124C>T		intron	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.-35-124C>T		intron	N/A	ENSP00000436962.1	P46977-1
	STT3A	ENST00000534472.5	TSL:1	n.101-124C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3521 AN: 152160 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00435 AC: 1984 AN: 456040 Hom.: 45 AF XY: 0.00379 AC XY: 915 AN XY: 241306

African (AFR) AF: 0.0749 AC: 901 AN: 12024

American (AMR) AF: 0.00622 AC: 117 AN: 18796

Ashkenazi Jewish (ASJ) AF: 0.00188 AC: 26 AN: 13850

East Asian (EAS) AF: 0.0165 AC: 507 AN: 30654

South Asian (SAS) AF: 0.00179 AC: 81 AN: 45360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34102

Middle Eastern (MID) AF: 0.00947 AC: 20 AN: 2112

European-Non Finnish (NFE) AF: 0.000509 AC: 139 AN: 273002

Other (OTH) AF: 0.00738 AC: 193 AN: 26140

GnomAD4 genome AF: 0.0232 AC: 3531 AN: 152278 Hom.: 125 Cov.: 32 AF XY: 0.0226 AC XY: 1684 AN XY: 74480

African (AFR) AF: 0.0773 AC: 3212 AN: 41550

American (AMR) AF: 0.00902 AC: 138 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.0193 AC: 100 AN: 5186

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68018

Other (OTH) AF: 0.0156 AC: 33 AN: 2110

Alfa AF: 0.0147 Hom.: 29

Bravo AF: 0.0264

Asia WGS AF: 0.0220 AC: 77 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	-0.97
CADD	Benign	0.41
DANN	Benign	0.71
PhyloP100		-1.5
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: rs10082593; hg19: chr11-125465652;