12-122207320-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_030765.4(B3GNT4):c.1069T>G(p.Trp357Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,611,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
B3GNT4
NM_030765.4 missense
NM_030765.4 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 2.67
Genes affected
B3GNT4 (HGNC:15683): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase protein family. The encoded enzyme is involved in the biosynthesis of poly-N-acetyllactosamine chains and prefers lacto-N-neotetraose as a substrate. It is a type II transmembrane protein. [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, 0.777
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
B3GNT4 | NM_030765.4 | c.1069T>G | p.Trp357Gly | missense_variant | 3/3 | ENST00000324189.5 | |
B3GNT4 | NM_001330492.2 | c.994T>G | p.Trp332Gly | missense_variant | 2/2 | ||
B3GNT4 | XM_047429535.1 | c.994T>G | p.Trp332Gly | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
B3GNT4 | ENST00000324189.5 | c.1069T>G | p.Trp357Gly | missense_variant | 3/3 | 1 | NM_030765.4 | A2 | |
B3GNT4 | ENST00000535274.1 | c.994T>G | p.Trp332Gly | missense_variant | 1/1 | P2 | |||
B3GNT4 | ENST00000546192.1 | c.994T>G | p.Trp332Gly | missense_variant | 2/2 | 2 | P2 | ||
B3GNT4 | ENST00000545141.1 | n.74-376T>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD4 exome AF: 0.0000206 AC: 30AN: 1458946Hom.: 0 Cov.: 34 AF XY: 0.0000207 AC XY: 15AN XY: 725474
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74328
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ExAC
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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 | Feb 13, 2024 | The c.1069T>G (p.W357G) alteration is located in exon 3 (coding exon 2) of the B3GNT4 gene. This alteration results from a T to G substitution at nucleotide position 1069, causing the tryptophan (W) at amino acid position 357 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at