Variant 11-77039726-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138706.5(B3GNT6):c.175G>A(p.Glu59Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,605,436 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

B3GNT6
NM_138706.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.205

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:

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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=0.0039001107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GNT6	NM_138706.5 linkuse as main transcript	c.175G>A	p.Glu59Lys	missense_variant	2/2	ENST00000622824.1	NP_619651.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GNT6	ENST00000622824.1 linkuse as main transcript	c.175G>A	p.Glu59Lys	missense_variant	2/2	1	NM_138706.5	ENSP00000484640	P1	Q6ZMB0-1
B3GNT6	ENST00000528622.5 linkuse as main transcript	c.175G>A	p.Glu59Lys	missense_variant	3/3	3		ENSP00000435628

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000439

AC:

AN:

225442

Hom.:

AF XY:

0.000385

AC XY:

AN XY:

124642

show subpopulations

Gnomad AFR exome

AF:

0.000233

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00789

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000201

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.000232

AC:

337

AN:

1453128

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

166

AN XY:

722534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000905

Gnomad4 AMR exome

AF:

0.000182

Gnomad4 ASJ exome

AF:

0.00778

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000703

Gnomad4 OTH exome

AF:

0.000401

GnomAD4 genome

AF:

0.000230

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000785

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.000329

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 21, 2021

The c.175G>A (p.E59K) alteration is located in exon 2 (coding exon 1) of the B3GNT6 gene. This alteration results from a G to A substitution at nucleotide position 175, causing the glutamic acid (E) at amino acid position 59 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.3

DANN

Benign

0.82

DEOGEN2

Benign

0.0017

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.31

N;.

REVEL

Benign

0.072

Sift

Benign

0.90

T;.

Sift4G

Benign

0.92

T;T

Polyphen

0.0

.;B

Vest4

0.12

MutPred

0.27

Gain of ubiquitination at E59 (P = 0.0029);Gain of ubiquitination at E59 (P = 0.0029);

MVP

0.21

ClinPred

0.0013

GERP RS

-1.6

Varity_R

0.029

gMVP

0.58

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