rs76400963

Positions:

• chr3-31596870-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_178862.3(STT3B):​c.777+7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,606,354 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 32)
  • Exomes 𝑓: 0.014 (207 hom.)
• Consequence: STT3B NM_178862.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001948
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0360

Genes affected

STT3B (HGNC:30611): (STT3 oligosaccharyltransferase complex catalytic subunit B) The protein encoded by this gene is a catalytic subunit of a protein complex that transfers oligosaccharides onto asparagine residues. Defects in this gene are a cause of congenital disorder of glycosylation Ix (CDG1X). [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 3-31596870-T-G is Benign according to our data. Variant chr3-31596870-T-G is described in ClinVar as [Benign]. Clinvar id is 380194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0125 (1898/152280) while in subpopulation NFE AF= 0.0192 (1304/68016). AF 95% confidence interval is 0.0183. There are 20 homozygotes in gnomad4. There are 925 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STT3B	NM_178862.3	c.777+7T>G		splice_region_variant, intron_variant		ENST00000295770.4
STT3B	XM_011533465.2	c.777+7T>G		splice_region_variant, intron_variant
STT3B	XM_017005858.2	c.339+7T>G		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STT3B	ENST00000295770.4	c.777+7T>G		splice_region_variant, intron_variant		1	NM_178862.3	P1

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1898 AN: 152162 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.0133 AC: 3321 AN: 249996 Hom.: 46 AF XY: 0.0136 AC XY: 1831 AN XY: 135114

Gnomad AFR exome AF: 0.00253

Gnomad AMR exome AF: 0.00423

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00290

Gnomad FIN exome AF: 0.0320

Gnomad NFE exome AF: 0.0190

Gnomad OTH exome AF: 0.0150

GnomAD4 exome AF: 0.0141 AC: 20457 AN: 1454074 Hom.: 207 Cov.: 28 AF XY: 0.0140 AC XY: 10105 AN XY: 723822

Gnomad4 AFR exome AF: 0.00165

Gnomad4 AMR exome AF: 0.00484

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00273

Gnomad4 FIN exome AF: 0.0309

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0125 AC: 1898 AN: 152280 Hom.: 20 Cov.: 32 AF XY: 0.0124 AC XY: 925 AN XY: 74452

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.0309

Gnomad4 NFE AF: 0.0192

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0175 Hom.: 20

Bravo AF: 0.00931

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0123

EpiControl AF: 0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 12, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

STT3B-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

STT3B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 23, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.1
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.10		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

Other links and lift over

dbSNP: rs76400963; hg19: chr3-31638362;