11-134383907-G-A

Variant names:

• chr11-134383907-G-A
• rs766176210
• NM_054025.3:c.394C>T

Variant summary

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

The NM_054025.3(B3GAT1):​c.394C>T​(p.Arg132Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,443,154 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R132G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: B3GAT1 NM_054025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52
• Publications: 2 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.394C>T	p.Arg132Cys	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.394C>T	p.Arg132Cys	missense_variant	Exon 3 of 6	1	NM_054025.3	ENSP00000307875.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000897 AC: 2 AN: 222996 AF XY: 0.00000816

Gnomad AFR exome AF: 0.00

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: 0.0000198

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1443154 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717718

African (AFR) AF: 0.00 AC: 0 AN: 33250

American (AMR) AF: 0.00 AC: 0 AN: 44042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25844

East Asian (EAS) AF: 0.00 AC: 0 AN: 39210

South Asian (SAS) AF: 0.00 AC: 0 AN: 85424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1107544

Other (OTH) AF: 0.00 AC: 0 AN: 59818

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000169 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.87	D;D;D
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;.;.
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.8	M;M;M
PhyloP100		4.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.017	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.68
MVP		0.47
MPC		2.1
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.78
gMVP		0.88
Mutation Taster		=37/63	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

dbSNP: rs766176210; hg19: chr11-134253801;