Genetic Variant STT3B:p.Pro55Ala (chr3-31533161-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178862.3(STT3B):c.163C>G(p.Pro55Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,303,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

STT3B
NM_178862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.187

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12570152).

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.163C>G	p.Pro55Ala	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.163C>G	p.Pro55Ala	missense	Exon 1 of 16	ENSP00000295770.2	Q8TCJ2
STT3B	ENST00000453168.5	TSL:1	n.524C>G		non_coding_transcript_exon	Exon 1 of 10
STT3B	ENST00000935233.1		c.163C>G	p.Pro55Ala	missense	Exon 1 of 16	ENSP00000605292.1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000484

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

28796

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1152330

Hom.:

Cov.:

AF XY:

0.0000161

AC XY:

AN XY:

557436

show subpopulations

African (AFR)

AF:

0.000526

AC:

AN:

22826

American (AMR)

AF:

0.000112

AC:

AN:

8952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15472

East Asian (EAS)

AF:

0.00

AC:

AN:

25982

South Asian (SAS)

AF:

0.00

AC:

AN:

34552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38160

Middle Eastern (MID)

AF:

0.000289

AC:

AN:

3458

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

957238

Other (OTH)

AF:

0.00

AC:

AN:

45690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.000132

AC:

AN:

151206

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73796

show subpopulations

African (AFR)

AF:

0.000484

AC:

AN:

41282

American (AMR)

AF:

0.00

AC:

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67700

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.000147

ExAC

AF:

0.0000189

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

0.048

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.077

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.19

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.31

REVEL

Benign

0.086

Sift

Benign

0.30

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.22

MutPred

0.22

Loss of glycosylation at P51 (P = 0.0033)

MVP

0.13

MPC

0.82

ClinPred

0.12

GERP RS

3.4

PromoterAI

-0.0047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.11

gMVP

0.20

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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