Genetic Variant STT3A:c.-36+853C>T (chr11-125592740-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.23

Variant links:

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]

STT3A links:

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]

FEZ1 links:

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

STT3A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STT3A	NM_152713.5 link	c.-214C>T		upstream_gene_variant		ENST00000392708.9	NP_689926.1	P46977-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STT3A	ENST00000392708.9 link	c.-214C>T		upstream_gene_variant		1	NM_152713.5	ENSP00000376472.3		P46977-1

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8524

AN:

152100

Hom.:

302

Cov.:

show subpopulations

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.:

AF XY:

0.0615

AC XY:

5003

AN XY:

81410

show subpopulations

Gnomad4 AFR exome

AF:

0.0268

Gnomad4 AMR exome

AF:

0.0394

Gnomad4 ASJ exome

AF:

0.0529

Gnomad4 EAS exome

AF:

0.000959

Gnomad4 SAS exome

AF:

0.0425

Gnomad4 FIN exome

AF:

0.0582

Gnomad4 NFE exome

AF:

0.0804

Gnomad4 OTH exome

AF:

0.0751

GnomAD4 genome

AF:

0.0560

AC:

8531

AN:

152220

Hom.:

304

Cov.:

AF XY:

0.0540

AC XY:

4022

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0265

Gnomad4 AMR

AF:

0.0509

Gnomad4 ASJ

AF:

0.0560

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.0416

Gnomad4 FIN

AF:

0.0501

Gnomad4 NFE

AF:

0.0784

Gnomad4 OTH

AF:

0.0686

Alfa

AF:

0.0177

Hom.:

Bravo

AF:

0.0553

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.75

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over