chr11-125591814-A-G

Variant names:

• chr11-125591814-A-G
• rs548181
• ENST00000527606.5:c.-109A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000527606.5(STT3A):​c.-109A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,326 control chromosomes in the GnomAD database, including 53,295 homozygotes. 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 0.83 (53210 hom., cov: 31)
  • Exomes 𝑓: 0.92 (85 hom.)
• Consequence: STT3A ENST00000527606.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 38 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.919 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3A-AS1	NR_132372.1		n.151+604T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3A	ENST00000527606.5	TSL:4	c.-109A>G		5_prime_UTR	Exon 1 of 5	ENSP00000436558.1
	FEZ1	ENST00000648911.1		c.-259+604T>C		intron	N/A	ENSP00000497070.1
	FEZ1	ENST00000530526.1	TSL:3	n.151+604T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126614 AN: 152006 Hom.: 53175 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.854

GnomAD4 exome AF: 0.916 AC: 185 AN: 202 Hom.: 85 Cov.: 0 AF XY: 0.934 AC XY: 114 AN XY: 122

African (AFR) AF: 0.667 AC: 4 AN: 6

American (AMR) AF: 1.00 AC: 4 AN: 4

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 0.833 AC: 5 AN: 6

South Asian (SAS) AF: 1.00 AC: 48 AN: 48

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.881 AC: 104 AN: 118

Other (OTH) AF: 1.00 AC: 10 AN: 10

GnomAD4 genome AF: 0.833 AC: 126697 AN: 152124 Hom.: 53210 Cov.: 31 AF XY: 0.832 AC XY: 61847 AN XY: 74346

African (AFR) AF: 0.714 AC: 29608 AN: 41492

American (AMR) AF: 0.857 AC: 13112 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3049 AN: 3470

East Asian (EAS) AF: 0.884 AC: 4564 AN: 5164

South Asian (SAS) AF: 0.942 AC: 4548 AN: 4828

European-Finnish (FIN) AF: 0.815 AC: 8608 AN: 10560

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60336 AN: 68004

Other (OTH) AF: 0.855 AC: 1805 AN: 2110

Alfa AF: 0.872 Hom.: 229675

Bravo AF: 0.827

Asia WGS AF: 0.887 AC: 3084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-1.7
PromoterAI		-0.0072	Neutral

Splicing

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

Other links and lift over

dbSNP: rs548181; hg19: chr11-125461709;