Genetic Variant NM_178862.3:c.109G>C (chr3-31533107-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178862.3(STT3B):c.109G>C(p.Gly37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,412,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. G37G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

STT3B
NM_178862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

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

STT3B links:

ENSG00000288926 (HGNC:):

ENSG00000288926 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16927859).

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.109G>C	p.Gly37Arg	missense	Exon 1 of 16	NP_849193.1	Q8TCJ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STT3B	ENST00000295770.4	TSL:1 MANE Select	c.109G>C	p.Gly37Arg	missense	Exon 1 of 16	ENSP00000295770.2	Q8TCJ2
STT3B	ENST00000453168.5	TSL:1	n.470G>C		non_coding_transcript_exon	Exon 1 of 10
STT3B	ENST00000935233.1		c.109G>C	p.Gly37Arg	missense	Exon 1 of 16	ENSP00000605292.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000387

AC:

AN:

77510

AF XY:

0.0000219

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000858

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1261106

Hom.:

Cov.:

AF XY:

0.0000258

AC XY:

AN XY:

620582

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25588

American (AMR)

AF:

0.00

AC:

AN:

16694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19272

East Asian (EAS)

AF:

0.00

AC:

AN:

29696

South Asian (SAS)

AF:

0.00

AC:

AN:

55320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4552

European-Non Finnish (NFE)

AF:

0.0000354

AC:

AN:

1015728

Other (OTH)

AF:

0.0000394

AC:

AN:

50704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000132

AC:

AN:

151282

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41284

American (AMR)

AF:

0.00

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5078

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67756

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000264

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.89

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

1.1

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.74

REVEL

Benign

0.064

Sift

Benign

0.097

Sift4G

Uncertain

0.0090

Polyphen

0.0

Vest4

0.088

MutPred

0.36

Gain of MoRF binding (P = 0.0078)

MVP

0.068

MPC

2.1

ClinPred

0.18

GERP RS

2.1

PromoterAI

0.0016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.66

Mutation Taster

=79/21

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over