Genetic Variant B3GAT2:p.Pro151Ala (chr6-70955979-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_080742.3(B3GAT2):c.451C>G(p.Pro151Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,310,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

B3GAT2
NM_080742.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

Publications

0 publications found

Variant links:

Genes affected

B3GAT2 (HGNC:922): (beta-1,3-glucuronyltransferase 2) The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes the transfer of a beta-1,3 linked glucuronic acid to a terminal galactose in different glycoproteins or glycolipids containing a Gal-beta-1-4GlcNAc or Gal-beta-1-3GlcNAc residue. The encoded protein is involved in the synthesis of the human natural killer-1 (HNK-1) carbohydrate epitope, a sulfated trisaccharide implicated in cellular migration and adhesion in the nervous system. [provided by RefSeq, Jul 2008]

B3GAT2 links:

ENSG00000293752 (HGNC:):

ENSG00000293752 links:

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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=0.14867172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GAT2	NM_080742.3 link	c.451C>G	p.Pro151Ala	missense_variant	Exon 1 of 4	ENST00000230053.11	NP_542780.1	Q9NPZ5
B3GAT2	XM_047418209.1 link	c.451C>G	p.Pro151Ala	missense_variant	Exon 1 of 3		XP_047274165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
B3GAT2	ENST00000230053.11 link	c.451C>G	p.Pro151Ala	missense_variant	Exon 1 of 4	1	NM_080742.3	ENSP00000230053.6	Q9NPZ5
B3GAT2	ENST00000615536.1 link	c.375+76C>G		intron_variant	Intron 1 of 3	1		ENSP00000481320.1	A0A087WXU9
ENSG00000293752	ENST00000718740.1 link	n.-149G>C		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.63e-7

AC:

AN:

1310200

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

643544

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25594

American (AMR)

AF:

0.00

AC:

AN:

18468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19450

East Asian (EAS)

AF:

0.00

AC:

AN:

30816

South Asian (SAS)

AF:

0.00

AC:

AN:

66020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5030

European-Non Finnish (NFE)

AF:

9.54e-7

AC:

AN:

1047750

Other (OTH)

AF:

0.00

AC:

AN:

53946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.451C>G (p.P151A) alteration is located in exon 1 (coding exon 1) of the B3GAT2 gene. This alteration results from a C to G substitution at nucleotide position 451, causing the proline (P) at amino acid position 151 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.068

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.78

M_CAP

Benign

0.078

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

1.9

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.59

REVEL

Benign

0.050

Sift

Benign

0.10

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.090

MutPred

0.34

Gain of MoRF binding (P = 0.0422);

MVP

0.71

MPC

0.54

ClinPred

0.35

GERP RS

4.3

PromoterAI

-0.0090

Neutral

(source)

Varity_R

0.12

gMVP

0.37

Mutation Taster

=73/27

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over