rs76400963

Variant names:

• chr3-31596870-T-G
• rs76400963
• NM_178862.3:c.777+7T>G

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: 0.0360
• Publications: 2 publications found

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]

STT3B Gene-Disease associations (from GenCC):

• STT3B-congenital disorder of glycosylation

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178862.3. 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
	STT3B	NM_178862.3	MANE Select	c.777+7T>G		splice_region intron	N/A	NP_849193.1	Q8TCJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3B	ENST00000295770.4	TSL:1 MANE Select	c.777+7T>G		splice_region intron	N/A	ENSP00000295770.2	Q8TCJ2
	STT3B	ENST00000453168.5	TSL:1	n.1138+7T>G		splice_region intron	N/A
	STT3B	ENST00000935233.1		c.777+7T>G		splice_region intron	N/A	ENSP00000605292.1

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

GnomAD2 exomes AF: 0.0133 AC: 3321 AN: 249996 AF XY: 0.0136

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 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

African (AFR) AF: 0.00165 AC: 55 AN: 33304

American (AMR) AF: 0.00484 AC: 215 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 308 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00273 AC: 234 AN: 85846

European-Finnish (FIN) AF: 0.0309 AC: 1640 AN: 53066

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5752

European-Non Finnish (NFE) AF: 0.0156 AC: 17269 AN: 1105934

Other (OTH) AF: 0.0121 AC: 726 AN: 60102

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

African (AFR) AF: 0.00262 AC: 109 AN: 41572

American (AMR) AF: 0.00543 AC: 83 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4828

European-Finnish (FIN) AF: 0.0309 AC: 328 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0192 AC: 1304 AN: 68016

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	STT3B-congenital disorder of glycosylation (1)
-	-	1	STT3B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.1
DANN	Benign	0.72
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs76400963;

hg19: chr3-31638362;