11-77039678-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138706.5(B3GNT6):​c.127C>G​(p.Pro43Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,612,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

B3GNT6
NM_138706.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.592
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02100578).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
B3GNT6NM_138706.5 linkc.127C>G p.Pro43Ala 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.127C>G p.Pro43Ala missense_variant Exon 2 of 2 1 NM_138706.5 ENSP00000484640.1 Q6ZMB0-1
B3GNT6ENST00000528622.5 linkc.127C>G p.Pro43Ala missense_variant Exon 3 of 3 3 ENSP00000435628.1 E9PJ79

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000234
AC:
57
AN:
243768
Hom.:
0
AF XY:
0.000233
AC XY:
31
AN XY:
133010
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000582
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000140
Gnomad NFE exome
AF:
0.000479
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000139
AC:
203
AN:
1460284
Hom.:
0
Cov.:
30
AF XY:
0.000143
AC XY:
104
AN XY:
726454
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000759
Gnomad4 NFE exome
AF:
0.000166
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152328
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000251
Hom.:
0
Bravo
AF:
0.000125
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000366
AC:
3
ExAC
AF:
0.000306
AC:
37
EpiCase
AF:
0.000164
EpiControl
AF:
0.000297

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.127C>G (p.P43A) alteration is located in exon 2 (coding exon 1) of the B3GNT6 gene. This alteration results from a C to G substitution at nucleotide position 127, causing the proline (P) at amino acid position 43 to be replaced by an alanine (A). 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
0.056
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
3.4
DANN
Benign
0.40
DEOGEN2
Benign
0.0021
.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.37
T;T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.021
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.21
N;.
REVEL
Benign
0.071
Sift
Benign
0.49
T;.
Sift4G
Benign
0.56
T;T
Polyphen
0.0010
.;B
Vest4
0.12
MVP
0.13
ClinPred
0.036
T
GERP RS
0.23
Varity_R
0.18
gMVP
0.42

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: rs373996731; hg19: chr11-76750722; API