11-125592740-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000527606.5(STT3A):​c.-36+853C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STT3A ENST00000527606.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

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>G		upstream_gene	N/A	NP_689926.1	P46977-1
	STT3A	NM_001278503.2		c.-302C>G		upstream_gene	N/A	NP_001265432.1	P46977-1
	STT3A	NM_001278504.2		c.-367C>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+853C>G		intron	N/A	ENSP00000436558.1	E9PI32
	STT3A	ENST00000392708.9	TSL:1 MANE Select	c.-214C>G		upstream_gene	N/A	ENSP00000376472.3	P46977-1
	STT3A	ENST00000529196.5	TSL:1	c.-302C>G		upstream_gene	N/A	ENSP00000436962.1	P46977-1

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 145724 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81470

African (AFR) AF: 0.00 AC: 0 AN: 3700

American (AMR) AF: 0.00 AC: 0 AN: 7196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3010

East Asian (EAS) AF: 0.00 AC: 0 AN: 5216

South Asian (SAS) AF: 0.00 AC: 0 AN: 33678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 78902

Other (OTH) AF: 0.00 AC: 0 AN: 6782

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74312

African (AFR) AF: 0.000290 AC: 12 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.9
DANN	Benign	0.61
PhyloP100		1.2
PromoterAI		0.14	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;