19-17808049-A-G

Position:

chr19-17808049-A-G

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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 made for transcript

Verdict is Likely_benign. Variant got -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 id is 3132569.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
B3GNT3	NM_014256.4 linkuse as main transcript	c.242A>G	p.Gln81Arg	missense_variant	2/3	ENST00000318683.7	NP_055071.2
B3GNT3	XM_011527626.3 linkuse as main transcript	c.242A>G	p.Gln81Arg	missense_variant	2/3		XP_011525928.1
B3GNT3	XM_047438042.1 linkuse as main transcript	c.242A>G	p.Gln81Arg	missense_variant	2/3		XP_047293998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
B3GNT3	ENST00000318683.7 linkuse as main transcript	c.242A>G	p.Gln81Arg	missense_variant	2/3	1	NM_014256.4	ENSP00000321874	P1
B3GNT3	ENST00000595387.1 linkuse as main transcript	c.242A>G	p.Gln81Arg	missense_variant	2/3	1		ENSP00000472638	P1
B3GNT3	ENST00000599265.5 linkuse as main transcript	c.242A>G	p.Gln81Arg	missense_variant	2/3	3		ENSP00000471733
B3GNT3	ENST00000600777.1 linkuse as main transcript	c.242A>G	p.Gln81Arg	missense_variant	2/2	3		ENSP00000468914

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

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250306

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135554

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000615

AC:

AN:

146418

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

70822

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:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.23

DANN

Benign

0.18

DEOGEN2

Benign

0.0029

T;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.34

T;.;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.46

.;N;.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.11

.;N;.;.

REVEL

Benign

0.042

Sift

Benign

0.85

.;T;.;.

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.028, 0.029

MVP

0.23

MPC

0.73

ClinPred

0.011

GERP RS

1.2

Varity_R

0.020

gMVP

0.59

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