chr11-125592730-G-T

Variant names:

• chr11-125592730-G-T
• rs12270381
• ENST00000527606.5:c.-36+843G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000527606.5(STT3A):​c.-36+843G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 296,812 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (147 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (13 hom.)
• Consequence: STT3A ENST00000527606.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0680
• 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]

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-125592730-G-T is Benign according to our data. Variant chr11-125592730-G-T is described in ClinVar as Benign. ClinVar VariationId is 1225504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 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.-224G>T		upstream_gene	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.-312G>T		upstream_gene	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-377G>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+843G>T		intron	N/A	ENSP00000436558.1	E9PI32
	STT3A	ENST00000392708.9	TSL:1 MANE Select	c.-224G>T		upstream_gene	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.-312G>T		upstream_gene	N/A	ENSP00000436962.1	P46977-1

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3732 AN: 152126 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00315 AC: 456 AN: 144568 Hom.: 13 Cov.: 0 AF XY: 0.00300 AC XY: 243 AN XY: 81060

African (AFR) AF: 0.0825 AC: 289 AN: 3504

American (AMR) AF: 0.00465 AC: 33 AN: 7092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2916

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5068

South Asian (SAS) AF: 0.00211 AC: 71 AN: 33612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6722

Middle Eastern (MID) AF: 0.00224 AC: 1 AN: 446

European-Non Finnish (NFE) AF: 0.000382 AC: 30 AN: 78524

Other (OTH) AF: 0.00464 AC: 31 AN: 6684

GnomAD4 genome AF: 0.0246 AC: 3745 AN: 152244 Hom.: 147 Cov.: 32 AF XY: 0.0232 AC XY: 1729 AN XY: 74454

African (AFR) AF: 0.0835 AC: 3468 AN: 41546

American (AMR) AF: 0.0114 AC: 174 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68006

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.00367 Hom.: 1

Bravo AF: 0.0279

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

ClinVar submissions

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	-0.76
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		0.068
PromoterAI		0.0024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12270381; hg19: chr11-125462625;