Genetic Variant B3GNT6:p.Pro69Ser (chr11-77039756-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_138706.5(B3GNT6):c.205C>T(p.Pro69Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,594,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

B3GNT6
NM_138706.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Trascript score misZ: -2.0224 (below the threshold of 3.09).

BP4

Computational evidence support a benign effect (MetaRNN=0.026329517).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138706.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT6	NM_138706.5	MANE Select	c.205C>T	p.Pro69Ser	missense	Exon 2 of 2	NP_619651.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B3GNT6	ENST00000622824.1	TSL:1 MANE Select	c.205C>T	p.Pro69Ser	missense	Exon 2 of 2	ENSP00000484640.1	Q6ZMB0-1
B3GNT6	ENST00000854987.1		c.205C>T	p.Pro69Ser	missense	Exon 2 of 2	ENSP00000525046.1
B3GNT6	ENST00000854988.1		c.205C>T	p.Pro69Ser	missense	Exon 2 of 2	ENSP00000525047.1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD2 exomes

AF:

0.0000626

AC:

AN:

207760

AF XY:

0.0000605

show subpopulations

Gnomad AFR exome

AF:

0.000782

Gnomad AMR exome

AF:

0.000128

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000298

AC:

AN:

1442260

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

716648

show subpopulations

African (AFR)

AF:

0.000851

AC:

AN:

32908

American (AMR)

AF:

0.0000944

AC:

AN:

42372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25830

East Asian (EAS)

AF:

0.00

AC:

AN:

38940

South Asian (SAS)

AF:

0.00

AC:

AN:

85124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46446

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00000452

AC:

AN:

1105262

Other (OTH)

AF:

0.0000838

AC:

AN:

59700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000269

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.000941

AC:

AN:

41458

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000456

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000844

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000428

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.45

M_CAP

Benign

0.0024

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

REVEL

Benign

0.013

Sift

Benign

0.23

Sift4G

Benign

0.063

Polyphen

0.025

Vest4

0.053

MVP

0.11

ClinPred

0.018

GERP RS

1.0

Varity_R

0.046

gMVP

0.53

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over