Genetic Variant NM_178862.3:c.87C>A (chr3-31533085-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_178862.3(STT3B):c.87C>A(p.Ser29Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,532 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S29S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

STT3B
NM_178862.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0950

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity STT3B_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16580069).

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.87C>A	p.Ser29Arg	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.87C>A	p.Ser29Arg	missense	Exon 1 of 16	ENSP00000295770.2	Q8TCJ2
STT3B	ENST00000453168.5	TSL:1	n.448C>A		non_coding_transcript_exon	Exon 1 of 10
STT3B	ENST00000935233.1		c.87C>A	p.Ser29Arg	missense	Exon 1 of 16	ENSP00000605292.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1382532

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28592

American (AMR)

AF:

0.00

AC:

AN:

33782

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23884

East Asian (EAS)

AF:

0.00

AC:

AN:

31712

South Asian (SAS)

AF:

0.00

AC:

AN:

77746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5458

European-Non Finnish (NFE)

AF:

9.30e-7

AC:

AN:

1075324

Other (OTH)

AF:

0.00

AC:

AN:

56350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.095

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.58

REVEL

Benign

0.083

Sift

Uncertain

0.013

Sift4G

Uncertain

0.010

Polyphen

0.0

Vest4

0.19

MutPred

0.14

Gain of MoRF binding (P = 0.0264)

MVP

0.13

MPC

0.94

ClinPred

0.78

GERP RS

2.5

PromoterAI

-0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.56

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over