11-125592740-C-T

Variant names:

• chr11-125592740-C-T
• rs11220140
• ENST00000527606.5:c.-36+853C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000527606.5(STT3A):​c.-36+853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 297,830 control chromosomes in the GnomAD database, including 688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (304 hom., cov: 32)
  • Exomes 𝑓: 0.064 (384 hom.)
• Consequence: STT3A ENST00000527606.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.23
• Publications: 4 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]

FEZ1 (HGNC:3659): (fasciculation and elongation protein zeta 1) This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Expression of this gene in C. elegans unc-76 mutants can restore to the mutants partial locomotion and axonal fasciculation, suggesting that it also functions in axonal outgrowth. The N-terminal half of the gene product is highly acidic. Alternatively spliced transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

STT3A-AS1 (HGNC:44585): (STT3A antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 11-125592740-C-T is Benign according to our data. Variant chr11-125592740-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527606.5. 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.-214C>T		upstream_gene	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.-302C>T		upstream_gene	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-367C>T		upstream_gene	N/A	NP_001265433.1	P46977-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3A	ENST00000527606.5	TSL:4	c.-36+853C>T		intron	N/A	ENSP00000436558.1	E9PI32
	STT3A	ENST00000392708.9	TSL:1 MANE Select	c.-214C>T		upstream_gene	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.-302C>T		upstream_gene	N/A	ENSP00000436962.1	P46977-1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8524 AN: 152100 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0560

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0698

GnomAD4 exome AF: 0.0637 AC: 9269 AN: 145610 Hom.: 384 Cov.: 0 AF XY: 0.0615 AC XY: 5003 AN XY: 81410

African (AFR) AF: 0.0268 AC: 99 AN: 3700

American (AMR) AF: 0.0394 AC: 283 AN: 7190

Ashkenazi Jewish (ASJ) AF: 0.0529 AC: 159 AN: 3008

East Asian (EAS) AF: 0.000959 AC: 5 AN: 5216

South Asian (SAS) AF: 0.0425 AC: 1430 AN: 33654

European-Finnish (FIN) AF: 0.0582 AC: 393 AN: 6758

Middle Eastern (MID) AF: 0.105 AC: 50 AN: 476

European-Non Finnish (NFE) AF: 0.0804 AC: 6341 AN: 78828

Other (OTH) AF: 0.0751 AC: 509 AN: 6780

GnomAD4 genome AF: 0.0560 AC: 8531 AN: 152220 Hom.: 304 Cov.: 32 AF XY: 0.0540 AC XY: 4022 AN XY: 74434

African (AFR) AF: 0.0265 AC: 1103 AN: 41546

American (AMR) AF: 0.0509 AC: 778 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0560 AC: 194 AN: 3464

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5176

South Asian (SAS) AF: 0.0416 AC: 201 AN: 4826

European-Finnish (FIN) AF: 0.0501 AC: 532 AN: 10610

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5329 AN: 67986

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.0177 Hom.: 12

Bravo AF: 0.0553

Asia WGS AF: 0.0260 AC: 91 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	-0.37
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		1.2
PromoterAI		-0.098	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11220140; hg19: chr11-125462635;