NM_014256.4:c.425G>T

Variant summary

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

The NM_014256.4(B3GNT3):​c.425G>T​(p.Arg142Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,218 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: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

B3GNT3
NM_014256.4 missense

Scores

4
9
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.26
Variant links:
Genes affected
B3GNT3 (HGNC:13528): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein and contains a signal anchor that is not cleaved. It prefers the substrates of lacto-N-tetraose and lacto-N-neotetraose, and is involved in the biosynthesis of poly-N-acetyllactosamine chains and the biosynthesis of the backbone structure of dimeric sialyl Lewis a. It plays dominant roles in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. [provided by RefSeq, Jul 2008]

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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, 0.835

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
B3GNT3NM_014256.4 linkc.425G>T p.Arg142Leu missense_variant Exon 2 of 3 ENST00000318683.7 NP_055071.2 Q9Y2A9
B3GNT3XM_011527626.3 linkc.425G>T p.Arg142Leu missense_variant Exon 2 of 3 XP_011525928.1 Q9Y2A9
B3GNT3XM_047438042.1 linkc.425G>T p.Arg142Leu missense_variant Exon 2 of 3 XP_047293998.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
B3GNT3ENST00000318683.7 linkc.425G>T p.Arg142Leu missense_variant Exon 2 of 3 1 NM_014256.4 ENSP00000321874.5 Q9Y2A9
B3GNT3ENST00000595387.1 linkc.425G>T p.Arg142Leu missense_variant Exon 2 of 3 1 ENSP00000472638.1 Q9Y2A9
B3GNT3ENST00000599265.5 linkc.425G>T p.Arg142Leu missense_variant Exon 2 of 3 3 ENSP00000471733.1 M0R199
B3GNT3ENST00000600777.1 linkc.*43G>T downstream_gene_variant 3 ENSP00000468914.1 M0QX58

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461218
Hom.:
0
Cov.:
36
AF XY:
0.00000138
AC XY:
1
AN XY:
726866
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000282
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;T;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.66
T;.;T
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.84
D;D;D
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.0
.;M;M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-5.4
.;D;.
REVEL
Uncertain
0.31
Sift
Uncertain
0.0020
.;D;.
Sift4G
Uncertain
0.037
D;D;D
Polyphen
0.97
.;D;D
Vest4
0.68, 0.68
MutPred
0.69
Loss of MoRF binding (P = 0.0117);Loss of MoRF binding (P = 0.0117);Loss of MoRF binding (P = 0.0117);
MVP
0.66
MPC
1.9
ClinPred
0.98
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.81
gMVP
0.94

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.

Other links and lift over

dbSNP: rs770788961; hg19: chr19-17919041; API