Genetic Variant STT3A:c.88+112T>G (chr11-125596115-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152713.5(STT3A):c.88+112T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 837,196 control chromosomes in the GnomAD database, including 2,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1219 hom., cov: 32)

Exomes 𝑓: 0.058 ( 1481 hom. )

Consequence

STT3A
NM_152713.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.762

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-125596115-T-G is Benign according to our data. Variant chr11-125596115-T-G is described in ClinVar as [Benign]. Clinvar id is 1244774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STT3A	NM_152713.5 link	c.88+112T>G		intron_variant	Intron 2 of 17	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.88+112T>G		intron_variant	Intron 2 of 17	1	NM_152713.5	ENSP00000376472.3		P46977-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16172

AN:

152050

Hom.:

1215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.0648

Gnomad ASJ

AF:

0.0783

Gnomad EAS

AF:

0.0215

Gnomad SAS

AF:

0.0552

Gnomad FIN

AF:

0.0438

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0673

Gnomad OTH

AF:

0.108

GnomAD4 exome

AF:

0.0583

AC:

39927

AN:

685028

Hom.:

1481

AF XY:

0.0569

AC XY:

20466

AN XY:

359372

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0457

Gnomad4 ASJ exome

AF:

0.0735

Gnomad4 EAS exome

AF:

0.0172

Gnomad4 SAS exome

AF:

0.0435

Gnomad4 FIN exome

AF:

0.0468

Gnomad4 NFE exome

AF:

0.0577

Gnomad4 OTH exome

AF:

0.0724

GnomAD4 genome

AF:

0.106

AC:

16202

AN:

152168

Hom.:

1219

Cov.:

AF XY:

0.103

AC XY:

7691

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.0647

Gnomad4 ASJ

AF:

0.0783

Gnomad4 EAS

AF:

0.0218

Gnomad4 SAS

AF:

0.0551

Gnomad4 FIN

AF:

0.0438

Gnomad4 NFE

AF:

0.0673

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0849

Hom.:

Bravo

AF:

0.114

Asia WGS

AF:

0.0600

AC:

207

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

Sep 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.1

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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