Genetic Variant B3GNT6:p.His100Tyr (chr11-77039849-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

B3GNT6
NM_138706.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.40

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.17643413).

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.298C>T	p.His100Tyr	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.298C>T	p.His100Tyr	missense	Exon 2 of 2	ENSP00000484640.1	Q6ZMB0-1
B3GNT6	ENST00000854987.1		c.298C>T	p.His100Tyr	missense	Exon 2 of 2	ENSP00000525046.1
B3GNT6	ENST00000854988.1		c.298C>T	p.His100Tyr	missense	Exon 2 of 2	ENSP00000525047.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

195292

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000140

AC:

AN:

1431816

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711648

show subpopulations

African (AFR)

AF:

0.0000608

AC:

AN:

32870

American (AMR)

AF:

0.00

AC:

AN:

42448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25738

East Asian (EAS)

AF:

0.00

AC:

AN:

38648

South Asian (SAS)

AF:

0.00

AC:

AN:

84148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104608

Other (OTH)

AF:

0.00

AC:

AN:

59562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.00

Hom.:

Bravo

AF:

0.0000151

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

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.67

M_CAP

Benign

0.0021

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

-1.4

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.5

REVEL

Benign

0.055

Sift

Benign

0.10

Sift4G

Uncertain

0.013

Polyphen

0.10

Vest4

0.088

MutPred

0.54

Loss of sheet (P = 0.1158)

MVP

0.44

ClinPred

0.14

GERP RS

3.4

Varity_R

0.096

gMVP

0.46

Mutation Taster

=94/6

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