chr11-77039849-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138706.5(B3GNT6):​c.298C>T​(p.His100Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,584,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

B3GNT6
NM_138706.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.40
Variant links:
Genes affected
B3GNT6 (HGNC:24141): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6) The protein encoded by this gene is a beta-1,3-N-acetylglucosaminyltransferase that adds an N-acetylglucosamine moiety to N-acetylgalactosamine-modified serine or threonine. The encoded enzyme is responsible for creating the core 3 structure of O-glycans, which are important components of mucin-type glycoproteins. [provided by RefSeq, Dec 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17643413).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
B3GNT6NM_138706.5 linkc.298C>T p.His100Tyr missense_variant Exon 2 of 2 ENST00000622824.1 NP_619651.3 Q6ZMB0-1A8K9Q8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
B3GNT6ENST00000622824.1 linkc.298C>T p.His100Tyr missense_variant Exon 2 of 2 1 NM_138706.5 ENSP00000484640.1 Q6ZMB0-1
B3GNT6ENST00000528622.5 linkc.298C>T p.His100Tyr missense_variant Exon 3 of 3 3 ENSP00000435628.1 E9PJ79

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152232
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1431816
Hom.:
0
Cov.:
30
AF XY:
0.00000141
AC XY:
1
AN XY:
711648
show subpopulations
Gnomad4 AFR exome
AF:
0.0000608
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
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
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.298C>T (p.H100Y) alteration is located in exon 2 (coding exon 1) of the B3GNT6 gene. This alteration results from a C to T substitution at nucleotide position 298, causing the histidine (H) at amino acid position 100 to be replaced by a tyrosine (Y). 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
Benign
0.13
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Benign
0.0053
.;T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.81
.;L
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.5
N;.
REVEL
Benign
0.055
Sift
Benign
0.10
T;.
Sift4G
Uncertain
0.013
D;T
Polyphen
0.10
.;B
Vest4
0.088
MutPred
0.54
Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP
0.44
ClinPred
0.14
T
GERP RS
3.4
Varity_R
0.096
gMVP
0.46

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: rs1555027474; hg19: chr11-76750893; API