11-134384014-G-C

Variant names:

• chr11-134384014-G-C
• rs766472299
• NM_054025.3:c.287C>G

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.287C>G​(p.Pro96Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,916 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P96L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: B3GAT1 NM_054025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.92
• 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, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GAT1	NM_054025.3	c.287C>G	p.Pro96Arg	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.287C>G	p.Pro96Arg	missense_variant	Exon 3 of 6	1	NM_054025.3	ENSP00000307875.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452916 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723156

African (AFR) AF: 0.0000299 AC: 1 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 86078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111034

Other (OTH) AF: 0.00 AC: 0 AN: 60232

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D;D;D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;.;.
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.3	M;M;M
PhyloP100		6.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.3	D;D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.021	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.88	P;P;P
Vest4		0.94
MVP		0.57
MPC		2.0
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.83
gMVP		0.97
Mutation Taster		=34/66	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: rs766472299; hg19: chr11-134253908;