Variant chr19-17808232-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014256.4(B3GNT3):c.425G>A(p.Arg142His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

B3GNT3
NM_014256.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.26

Variant links:

Genes affected

B3GNT3 (HGNC:13528): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein and contains a signal anchor that is not cleaved. It prefers the substrates of lacto-N-tetraose and lacto-N-neotetraose, and is involved in the biosynthesis of poly-N-acetyllactosamine chains and the biosynthesis of the backbone structure of dimeric sialyl Lewis a. It plays dominant roles in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. [provided by RefSeq, Jul 2008]

B3GNT3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT3	NM_014256.4 link	c.425G>A	p.Arg142His	missense_variant	Exon 2 of 3	ENST00000318683.7	NP_055071.2	Q9Y2A9
B3GNT3	XM_011527626.3 link	c.425G>A	p.Arg142His	missense_variant	Exon 2 of 3		XP_011525928.1	Q9Y2A9
B3GNT3	XM_047438042.1 link	c.425G>A	p.Arg142His	missense_variant	Exon 2 of 3		XP_047293998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
B3GNT3	ENST00000318683.7 link	c.425G>A	p.Arg142His	missense_variant	Exon 2 of 3	1	NM_014256.4	ENSP00000321874.5	Q9Y2A9
B3GNT3	ENST00000595387.1 link	c.425G>A	p.Arg142His	missense_variant	Exon 2 of 3	1		ENSP00000472638.1	Q9Y2A9
B3GNT3	ENST00000599265.5 link	c.425G>A	p.Arg142His	missense_variant	Exon 2 of 3	3		ENSP00000471733.1	M0R199
B3GNT3	ENST00000600777.1 link	c.*43G>A		downstream_gene_variant		3		ENSP00000468914.1	M0QX58

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248696

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

135006

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461218

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.425G>A (p.R142H) alteration is located in exon 2 (coding exon 1) of the B3GNT3 gene. This alteration results from a G to A substitution at nucleotide position 425, causing the arginine (R) at amino acid position 142 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.72

T;.;T

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.86

D;D;D

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.7

.;M;M

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.1

.;D;.

REVEL

Uncertain

0.48

Sift

Uncertain

0.0020

.;D;.

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.59, 0.59

MutPred

0.72

Loss of MoRF binding (P = 0.0143);Loss of MoRF binding (P = 0.0143);Loss of MoRF binding (P = 0.0143);

MVP

0.75

MPC

1.9

ClinPred

0.97

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.51

gMVP

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over