Variant 20-49639787-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_004776.4(B4GALT5):c.808G>A(p.Glu270Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

B4GALT5
NM_004776.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

B4GALT5 (HGNC:928): (beta-1,4-galactosyltransferase 5) This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. The function of the enzyme encoded by this gene is not clear. This gene was previously designated as B4GALT4 but was renamed to B4GALT5. In the literature it is also referred to as beta4GalT2. [provided by RefSeq, Jul 2008]

B4GALT5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.807

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B4GALT5	NM_004776.4 linkuse as main transcript	c.808G>A	p.Glu270Lys	missense_variant	7/9	ENST00000371711.4	NP_004767.1	O43286
B4GALT5	XM_047440587.1 linkuse as main transcript	c.676G>A	p.Glu226Lys	missense_variant	7/9		XP_047296543.1
B4GALT5	XM_047440588.1 linkuse as main transcript	c.676G>A	p.Glu226Lys	missense_variant	7/9		XP_047296544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B4GALT5	ENST00000371711.4 linkuse as main transcript	c.808G>A	p.Glu270Lys	missense_variant	7/9	1	NM_004776.4	ENSP00000360776.4		O43286

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251356

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460834

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726766

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.808G>A (p.E270K) alteration is located in exon 7 (coding exon 7) of the B4GALT5 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

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

Eigen

Benign

0.13

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.063

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.85

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.1

REVEL

Pathogenic

0.65

Sift

Benign

0.15

Sift4G

Benign

0.53

Polyphen

0.80

Vest4

0.80

MVP

0.59

MPC

2.3

ClinPred

0.61

GERP RS

5.2

Varity_R

0.22

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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