chr3-31596870-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Variant links:

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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

STT3B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
STT3B	NM_178862.3 link	c.777+7T>G	splice_region_variant, intron_variant	Intron 4 of 15	ENST00000295770.4	NP_849193.1	Q8TCJ2
STT3B	XM_017005858.2 link	c.339+7T>G	splice_region_variant, intron_variant	Intron 4 of 15		XP_016861347.1
STT3B	XM_011533465.2 link	c.777+7T>G	splice_region_variant, intron_variant	Intron 4 of 9		XP_011531767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STT3B	ENST00000295770.4 link	c.777+7T>G		splice_region_variant, intron_variant	Intron 4 of 15	1	NM_178862.3	ENSP00000295770.2		Q8TCJ2

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1898

AN:

152162

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0140

AC XY:

10105

AN XY:

723822

show subpopulations

African (AFR)

AF:

0.00165

AC:

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:

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:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0156

AC:

17269

AN:

1105934

Other (OTH)

AF:

0.0121

AC:

726

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

822

1645

2467

3290

4112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

570

1140

1710

2280

2850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0125

AC:

1898

AN:

152280

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

925

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00262

AC:

109

AN:

41572

American (AMR)

AF:

0.00543

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00352

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0309

AC:

328

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0192

AC:

1304

AN:

68016

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

101

201

302

402

503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.00931

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 12, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

STT3B-related disorder

Benign:1

Feb 23, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.72

PhyloP100

0.036

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over