11-134382841-G-A

Variant names:

• chr11-134382841-G-A
• rs1374536721
• NM_054025.3:c.787C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_054025.3(B3GAT1):​c.787C>T​(p.Arg263Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R263G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: B3GAT1 NM_054025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 1 publications found

Genes affected

B3GAT1 (HGNC:921): (beta-1,3-glucuronyltransferase 1) The protein encoded by this gene is a member of the glucuronyltransferase gene family. These enzymes exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product functions as the key enzyme in a glucuronyl transfer reaction during the biosynthesis of the carbohydrate epitope HNK-1 (human natural killer-1, also known as CD57 and LEU7). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GAT1	NM_054025.3	c.787C>T	p.Arg263Trp	missense_variant	Exon 4 of 6	ENST00000312527.9	NP_473366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GAT1	ENST00000312527.9	c.787C>T	p.Arg263Trp	missense_variant	Exon 4 of 6	1	NM_054025.3	ENSP00000307875.4
B3GAT1	ENST00000392580.5	c.787C>T	p.Arg263Trp	missense_variant	Exon 5 of 7	1		ENSP00000376359.1
B3GAT1	ENST00000531778.1	n.3684C>T		non_coding_transcript_exon_variant	Exon 2 of 4	1
B3GAT1	ENST00000524765.1	c.787C>T	p.Arg263Trp	missense_variant	Exon 4 of 6	2		ENSP00000433847.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251370 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000354 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;D;D
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.31	N
LIST_S2	Pathogenic	0.99	D;.;.
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.2	M;M;M
PhyloP100		0.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.029	B;B;B
Vest4		0.66
MVP		0.62
MPC		0.94
ClinPred		0.81	D
GERP RS		1.0
Varity_R		0.59
gMVP		0.94
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1374536721; hg19: chr11-134252735;