Genetic Variant B3GNT5:p.Glu270Lys (chr3-183270606-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032047.5(B3GNT5):c.808G>A(p.Glu270Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

B3GNT5
NM_032047.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19796428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT5	NM_032047.5 link	c.808G>A	p.Glu270Lys	missense_variant	Exon 2 of 2	ENST00000326505.4	NP_114436.1	Q9BYG0
MCF2L2	NM_015078.4 link	c.1862+6266C>T		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.808G>A	p.Glu270Lys	missense_variant	Exon 2 of 2	1	NM_032047.5	ENSP00000316173.3		Q9BYG0
MCF2L2	ENST00000328913.8 link	c.1862+6266C>T		intron_variant	Intron 15 of 29	5	NM_015078.4	ENSP00000328118.3		Q86YR7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251360

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135842

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727244

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:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.808G>A (p.E270K) alteration is located in exon 2 (coding exon 1) of the B3GNT5 gene. This alteration results from a G to A substitution at nucleotide position 808, causing the glutamic acid (E) at amino acid position 270 to be replaced by a lysine (K). 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

0.069

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;T;T

Eigen

Benign

-0.083

Eigen_PC

Benign

0.050

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

.;.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.69

N;N;N

REVEL

Benign

0.088

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.31

B;B;B

Vest4

0.35

MutPred

0.53

Gain of ubiquitination at E270 (P = 0.0289);Gain of ubiquitination at E270 (P = 0.0289);Gain of ubiquitination at E270 (P = 0.0289);

MVP

0.28

MPC

0.40

ClinPred

0.34

GERP RS

5.0

Varity_R

0.049

gMVP

0.56

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