chr19-17808220-G-T

Position:

• chr19-17808220-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014256.4(B3GNT3):​c.413G>T​(p.Gly138Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: B3GNT3 NM_014256.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.64

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GNT3	NM_014256.4	c.413G>T	p.Gly138Val	missense_variant	2/3	ENST00000318683.7
B3GNT3	XM_011527626.3	c.413G>T	p.Gly138Val	missense_variant	2/3
B3GNT3	XM_047438042.1	c.413G>T	p.Gly138Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GNT3	ENST00000318683.7	c.413G>T	p.Gly138Val	missense_variant	2/3	1	NM_014256.4	P1
B3GNT3	ENST00000595387.1	c.413G>T	p.Gly138Val	missense_variant	2/3	1		P1
B3GNT3	ENST00000599265.5	c.413G>T	p.Gly138Val	missense_variant	2/3	3
B3GNT3	ENST00000600777.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.413G>T (p.G138V) alteration is located in exon 2 (coding exon 1) of the B3GNT3 gene. This alteration results from a G to T substitution at nucleotide position 413, causing the glycine (G) at amino acid position 138 to be replaced by a valine (V). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;D;D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.57	T;.;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.8	.;H;H
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-7.2	.;D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	.;D;.
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.55, 0.55
MutPred		0.62		Loss of disorder (P = 0.0769);Loss of disorder (P = 0.0769);Loss of disorder (P = 0.0769);
MVP		0.72
MPC		1.9
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.74
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17919029;