Variant chr19-17807929-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014256.4(B3GNT3):c.122C>T(p.Pro41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,234 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: not found (cov: 30)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

B3GNT3
NM_014256.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.463

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10330698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
B3GNT3	NM_014256.4 linkuse as main transcript	c.122C>T	p.Pro41Leu	missense_variant	2/3	ENST00000318683.7	NP_055071.2
B3GNT3	XM_011527626.3 linkuse as main transcript	c.122C>T	p.Pro41Leu	missense_variant	2/3		XP_011525928.1
B3GNT3	XM_047438042.1 linkuse as main transcript	c.122C>T	p.Pro41Leu	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.122C>T	p.Pro41Leu	missense_variant	2/3	1	NM_014256.4	ENSP00000321874	P1
B3GNT3	ENST00000595387.1 linkuse as main transcript	c.122C>T	p.Pro41Leu	missense_variant	2/3	1		ENSP00000472638	P1
B3GNT3	ENST00000599265.5 linkuse as main transcript	c.122C>T	p.Pro41Leu	missense_variant	2/3	3		ENSP00000471733
B3GNT3	ENST00000600777.1 linkuse as main transcript	c.122C>T	p.Pro41Leu	missense_variant	2/2	3		ENSP00000468914

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000362

AC:

AN:

248596

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135142

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000716

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461234

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000495

AC:

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

Nov 29, 2021

The c.122C>T (p.P41L) alteration is located in exon 2 (coding exon 1) of the B3GNT3 gene. This alteration results from a C to T substitution at nucleotide position 122, causing the proline (P) at amino acid position 41 to be replaced by a leucine (L). 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

0.065

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.30

DANN

Benign

0.84

DEOGEN2

Benign

0.014

T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.49

T;.;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L;.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

.;N;.;.

REVEL

Benign

0.013

Sift

Benign

0.13

.;T;.;.

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.43

.;B;.;B

Vest4

0.067, 0.065

MutPred

0.33

Loss of catalytic residue at P40 (P = 0.0102);Loss of catalytic residue at P40 (P = 0.0102);Loss of catalytic residue at P40 (P = 0.0102);Loss of catalytic residue at P40 (P = 0.0102);

MVP

0.25

MPC

0.70

ClinPred

0.026

GERP RS

-7.3

Varity_R

0.030

gMVP

0.34

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