chr19-17811986-G-C

Position:

• chr19-17811986-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014256.4(B3GNT3):​c.983G>C​(p.Arg328Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R328H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GNT3 NM_014256.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077699095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GNT3	NM_014256.4	c.983G>C	p.Arg328Pro	missense_variant	3/3	ENST00000318683.7	NP_055071.2
B3GNT3	XM_011527626.3	c.983G>C	p.Arg328Pro	missense_variant	3/3		XP_011525928.1
B3GNT3	XM_047438042.1	c.983G>C	p.Arg328Pro	missense_variant	3/3		XP_047293998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GNT3	ENST00000318683.7	c.983G>C	p.Arg328Pro	missense_variant	3/3	1	NM_014256.4	ENSP00000321874.5
B3GNT3	ENST00000595387.1	c.983G>C	p.Arg328Pro	missense_variant	3/3	1		ENSP00000472638.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 92

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.4
DANN	Benign	0.83
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.20	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.0	D;.
REVEL	Benign	0.061
Sift	Benign	0.099	T;.
Sift4G	Benign	0.067	T;T
Polyphen		0.036	B;B
Vest4		0.094
MutPred		0.39		Gain of relative solvent accessibility (P = 0.0275);Gain of relative solvent accessibility (P = 0.0275);
MVP		0.26
MPC		1.4
ClinPred		0.11	T
GERP RS		3.1
Varity_R		0.24
gMVP		0.87

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

Other links and lift over

dbSNP: rs36686; hg19: chr19-17922795;