Genetic Variant NM_014256.4:c.242A>G (chr19-17808049-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014256.4(B3GNT3):c.242A>G(p.Gln81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000728 in 1,607,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000061 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

B3GNT3
NM_014256.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.66

Publications

0 publications found

Variant links:

Genes affected

B3GNT3 (HGNC:13528): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein and contains a signal anchor that is not cleaved. It prefers the substrates of lacto-N-tetraose and lacto-N-neotetraose, and is involved in the biosynthesis of poly-N-acetyllactosamine chains and the biosynthesis of the backbone structure of dimeric sialyl Lewis a. It plays dominant roles in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. [provided by RefSeq, Jul 2008]

B3GNT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038895905).

BP6

Variant 19-17808049-A-G is Benign according to our data. Variant chr19-17808049-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3132569.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014256.4. 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
	B3GNT3	NM_014256.4	MANE Select	c.242A>G	p.Gln81Arg	missense	Exon 2 of 3	NP_055071.2	Q9Y2A9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B3GNT3	ENST00000318683.7	TSL:1 MANE Select	c.242A>G	p.Gln81Arg	missense	Exon 2 of 3	ENSP00000321874.5	Q9Y2A9
B3GNT3	ENST00000595387.1	TSL:1	c.242A>G	p.Gln81Arg	missense	Exon 2 of 3	ENSP00000472638.1	Q9Y2A9
B3GNT3	ENST00000858455.1		c.242A>G	p.Gln81Arg	missense	Exon 2 of 3	ENSP00000528514.1

Frequencies

GnomAD3 genomes

AF:

0.0000615

AC:

AN:

146324

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

250306

AF XY:

0.0000221

show subpopulations

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:

0.0000443

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000739

AC:

108

AN:

1461472

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

727026

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000899

AC:

100

AN:

1111838

Other (OTH)

AF:

0.000116

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.0000615

AC:

AN:

146418

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

70822

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39388

American (AMR)

AF:

0.00

AC:

AN:

13842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

4914

South Asian (SAS)

AF:

0.00

AC:

AN:

4706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67502

Other (OTH)

AF:

0.00

AC:

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000847

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.052

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.23

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.34

M_CAP

Benign

0.013

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.46

PhyloP100

1.7

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.11

REVEL

Benign

0.042

Sift

Benign

0.85

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.028

MVP

0.23

MPC

0.73

ClinPred

0.011

GERP RS

1.2

Varity_R

0.020

gMVP

0.59

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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