chr11-125592720-T-G

Variant names:

• chr11-125592720-T-G
• rs115754046
• ENST00000527606.5:c.-36+833T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000527606.5(STT3A):​c.-36+833T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 291,446 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (26 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (1 hom.)
• Consequence: STT3A ENST00000527606.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.89
• 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 11-125592720-T-G is Benign according to our data. Variant chr11-125592720-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1329747.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.01 (1524/152274) while in subpopulation AFR AF = 0.0341 (1415/41554). AF 95% confidence interval is 0.0326. There are 26 homozygotes in GnomAd4. There are 712 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR,AD gene

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.-234T>G		upstream_gene	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.-322T>G		upstream_gene	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-387T>G		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+833T>G		intron	N/A	ENSP00000436558.1	E9PI32
	STT3A	ENST00000392708.9	TSL:1 MANE Select	c.-234T>G		upstream_gene	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.-322T>G		upstream_gene	N/A	ENSP00000436962.1	P46977-1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1523 AN: 152156 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.000984 AC: 137 AN: 139172 Hom.: 1 Cov.: 0 AF XY: 0.000792 AC XY: 62 AN XY: 78322

African (AFR) AF: 0.0318 AC: 108 AN: 3398

American (AMR) AF: 0.00117 AC: 8 AN: 6818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2804

East Asian (EAS) AF: 0.00 AC: 0 AN: 4850

South Asian (SAS) AF: 0.0000306 AC: 1 AN: 32708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 432

European-Non Finnish (NFE) AF: 0.000173 AC: 13 AN: 75362

Other (OTH) AF: 0.00110 AC: 7 AN: 6380

GnomAD4 genome AF: 0.0100 AC: 1524 AN: 152274 Hom.: 26 Cov.: 32 AF XY: 0.00956 AC XY: 712 AN XY: 74454

African (AFR) AF: 0.0341 AC: 1415 AN: 41554

American (AMR) AF: 0.00536 AC: 82 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68012

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00483 Hom.: 4

Bravo AF: 0.0117

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	0.073
DANN	Benign	0.43
PhyloP100		-3.9
PromoterAI		0.13	Neutral

Splicing

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

Other links and lift over

dbSNP: rs115754046; hg19: chr11-125462615;