11-134383691-G-A

Variant names:

• chr11-134383691-G-A
• NM_054025.3:c.610C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_054025.3(B3GAT1):​c.610C>T​(p.Leu204Phe) variant causes a missense change. 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: 33)
• Consequence: B3GAT1 NM_054025.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GAT1	NM_054025.3	c.610C>T	p.Leu204Phe	missense_variant	Exon 3 of 6	ENST00000312527.9	NP_473366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GAT1	ENST00000312527.9	c.610C>T	p.Leu204Phe	missense_variant	Exon 3 of 6	1	NM_054025.3	ENSP00000307875.4
B3GAT1	ENST00000392580.5	c.610C>T	p.Leu204Phe	missense_variant	Exon 4 of 7	1		ENSP00000376359.1
B3GAT1	ENST00000531778.1	n.3507C>T		non_coding_transcript_exon_variant	Exon 1 of 4	1
B3GAT1	ENST00000524765.1	c.610C>T	p.Leu204Phe	missense_variant	Exon 3 of 6	2		ENSP00000433847.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.610C>T (p.L204F) alteration is located in exon 3 (coding exon 2) of the B3GAT1 gene. This alteration results from a C to T substitution at nucleotide position 610, causing the leucine (L) at amino acid position 204 to be replaced by a phenylalanine (F). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D;D;D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;.
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.2	M;M;M
PhyloP100		6.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.83
MVP		0.65
MPC		2.1
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.90
gMVP		0.94
Mutation Taster		=14/86	disease causing

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

Other links and lift over

hg19: chr11-134253585;