Genetic Variant B3GNT5:p.Pro98Leu (chr3-183270091-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032047.5(B3GNT5):c.293C>T(p.Pro98Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,888 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: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

B3GNT5
NM_032047.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

B3GNT5 (HGNC:15684): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II membrane protein. It exhibits strong activity to transfer GlcNAc to glycolipid substrates and is identified as the most likely candidate for lactotriaosylceramide synthase. This enzyme is essential for the expression of Lewis X epitopes on glycolipids. [provided by RefSeq, Jul 2008]

B3GNT5 links:

MCF2L2 (HGNC:30319): (MCF.2 cell line derived transforming sequence-like 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

MCF2L2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT5	NM_032047.5 link	c.293C>T	p.Pro98Leu	missense_variant	Exon 2 of 2	ENST00000326505.4	NP_114436.1	Q9BYG0
MCF2L2	NM_015078.4 link	c.1862+6781G>A		intron_variant	Intron 15 of 29	ENST00000328913.8	NP_055893.4	Q86YR7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GNT5	ENST00000326505.4 link	c.293C>T	p.Pro98Leu	missense_variant	Exon 2 of 2	1	NM_032047.5	ENSP00000316173.3		Q9BYG0
MCF2L2	ENST00000328913.8 link	c.1862+6781G>A		intron_variant	Intron 15 of 29	5	NM_015078.4	ENSP00000328118.3		Q86YR7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251372

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS 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:

0.00000410

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.293C>T (p.P98L) alteration is located in exon 2 (coding exon 1) of the B3GNT5 gene. This alteration results from a C to T substitution at nucleotide position 293, causing the proline (P) at amino acid position 98 to be replaced by a leucine (L). 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

0.23

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D;D

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Benign

0.077

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.5

D;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.73

MutPred

0.57

Loss of glycosylation at P98 (P = 0.0349);Loss of glycosylation at P98 (P = 0.0349);Loss of glycosylation at P98 (P = 0.0349);

MVP

0.62

MPC

0.98

ClinPred

0.89

GERP RS

5.9

Varity_R

0.44

gMVP

0.90

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