6-33278326-C-T

Variant summary

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

The NM_003782.4(B3GALT4):​c.907C>T​(p.Leu303Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,104 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: 6.8e-7 ( 0 hom. )

Consequence

B3GALT4
NM_003782.4 missense

Scores

10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.136
Variant links:
Genes affected
B3GALT4 (HGNC:919): (beta-1,3-galactosyltransferase 4) 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). This gene is oriented telomere to centromere in close proximity to the ribosomal protein S18 gene. The functionality of the encoded protein is limited to ganglioseries glycolipid biosynthesis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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 UniProt
B3GALT4NM_003782.4 linkuse as main transcriptc.907C>T p.Leu303Phe missense_variant 1/1 ENST00000451237.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
B3GALT4ENST00000451237.3 linkuse as main transcriptc.907C>T p.Leu303Phe missense_variant 1/1 NM_003782.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460104
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151

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 submitterclinical testingAmbry GeneticsNov 21, 2023The c.907C>T (p.L303F) alteration is located in exon 1 (coding exon 1) of the B3GALT4 gene. This alteration results from a C to T substitution at nucleotide position 907, causing the leucine (L) at amino acid position 303 to be replaced by a phenylalanine (F). 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.82
D
M_CAP
Benign
0.081
D
MetaRNN
Uncertain
0.53
D
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.8
M
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.28
Sift
Uncertain
0.011
D
Sift4G
Uncertain
0.011
D
Polyphen
0.99
D
Vest4
0.27
MutPred
0.75
Gain of catalytic residue at L303 (P = 0.1091);
MVP
0.79
MPC
2.0
ClinPred
0.93
D
GERP RS
3.6
Varity_R
0.087
gMVP
0.91

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.

Other links and lift over

dbSNP: rs1765811815; hg19: chr6-33246103; API