Genetic Variant B3GNT6:p.Pro43Ala (chr11-77039678-C-G) – ACMG Classification: Likely_benign (-2 pts)

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

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]

B3GNT6 links:

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
B3GNT6	NM_138706.5 link	c.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
B3GNT6	ENST00000622824.1 link	c.127C>G	p.Pro43Ala	missense_variant	Exon 2 of 2	1	NM_138706.5	ENSP00000484640.1		Q6ZMB0-1
B3GNT6	ENST00000528622.5 link	c.127C>G	p.Pro43Ala	missense_variant	Exon 3 of 3	3		ENSP00000435628.1		E9PJ79

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152210

Hom.:

Cov.:

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:

AN:

243768

Hom.:

AF XY:

0.000233

AC XY:

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.:

Cov.:

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:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

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.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000366

AC:

ExAC

AF:

0.000306

AC:

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

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

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.37

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over