Variant 3-161086053-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003781.4(B3GALNT1):c.702C>G(p.Phe234Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,439,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

B3GALNT1
NM_003781.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.225

Variant links:

Genes affected

B3GALNT1 (HGNC:918): (beta-1,3-N-acetylgalactosaminyltransferase 1 (Globoside blood group)) This gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). The encoded protein of this gene does not use N-acetylglucosamine as an acceptor sugar at all. [provided by RefSeq, Mar 2017]

B3GALNT1 links:

B3GALNT1 (HGNC:):

B3GALNT1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALNT1	NM_003781.4 linkuse as main transcript	c.702C>G	p.Phe234Leu	missense_variant	5/5	ENST00000320474.10	NP_003772.1	O75752Q8TDY1Q7L9G8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALNT1	ENST00000320474.10 linkuse as main transcript	c.702C>G	p.Phe234Leu	missense_variant	5/5	1	NM_003781.4	ENSP00000323479.4		O75752

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000872

AC:

AN:

229404

Hom.:

AF XY:

0.0000162

AC XY:

AN XY:

123726

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:

0.0000395

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000942

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1439948

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

714754

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:

0.00000634

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Oct 26, 2022

The c.702C>G (p.F234L) alteration is located in exon 5 (coding exon 1) of the B3GALNT1 gene. This alteration results from a C to G substitution at nucleotide position 702, causing the phenylalanine (F) at amino acid position 234 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

D;D;D;D;D

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.69

.;.;.;.;T

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.68

D;D;D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

L;L;L;L;L

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.0

D;D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D;D

Polyphen

0.037

B;B;B;B;B

Vest4

0.42

MutPred

0.91

Loss of ubiquitination at K232 (P = 0.1113);Loss of ubiquitination at K232 (P = 0.1113);Loss of ubiquitination at K232 (P = 0.1113);Loss of ubiquitination at K232 (P = 0.1113);Loss of ubiquitination at K232 (P = 0.1113);

MVP

0.58

MPC

0.31

ClinPred

0.55

GERP RS

-1.5

Varity_R

0.52

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