chr19-17808232-G-T

Variant names:

• chr19-17808232-G-T
• rs770788961
• NM_014256.4:c.425G>T

Variant summary

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

The NM_014256.4(B3GNT3):​c.425G>T​(p.Arg142Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: B3GNT3 NM_014256.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

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, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT3	NM_014256.4	c.425G>T	p.Arg142Leu	missense_variant	Exon 2 of 3	ENST00000318683.7	NP_055071.2
B3GNT3	XM_011527626.3	c.425G>T	p.Arg142Leu	missense_variant	Exon 2 of 3		XP_011525928.1
B3GNT3	XM_047438042.1	c.425G>T	p.Arg142Leu	missense_variant	Exon 2 of 3		XP_047293998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GNT3	ENST00000318683.7	c.425G>T	p.Arg142Leu	missense_variant	Exon 2 of 3	1	NM_014256.4	ENSP00000321874.5
B3GNT3	ENST00000595387.1	c.425G>T	p.Arg142Leu	missense_variant	Exon 2 of 3	1		ENSP00000472638.1
B3GNT3	ENST00000599265.5	c.425G>T	p.Arg142Leu	missense_variant	Exon 2 of 3	3		ENSP00000471733.1
B3GNT3	ENST00000600777.1	c.*43G>T		downstream_gene_variant		3		ENSP00000468914.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461218 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726866

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T;.;T
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.0	.;M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.4	.;D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	.;D;.
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.97	.;D;D
Vest4		0.68, 0.68
MutPred		0.69		Loss of MoRF binding (P = 0.0117);Loss of MoRF binding (P = 0.0117);Loss of MoRF binding (P = 0.0117);
MVP		0.66
MPC		1.9
ClinPred		0.98	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.81
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs770788961; hg19: chr19-17919041;