11-134383778-G-A

Variant names:

• chr11-134383778-G-A
• rs1167877969
• NM_054025.3:c.523C>T

Variant summary

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

The NM_054025.3(B3GAT1):​c.523C>T​(p.Arg175Cys) 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. R175S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B3GAT1 NM_054025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• 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 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.523C>T	p.Arg175Cys	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.523C>T	p.Arg175Cys	missense_variant	Exon 3 of 6	1	NM_054025.3	ENSP00000307875.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 218476 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444372 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716876

African (AFR) AF: 0.00 AC: 0 AN: 33098

American (AMR) AF: 0.00 AC: 0 AN: 42956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.00 AC: 0 AN: 38808

South Asian (SAS) AF: 0.00 AC: 0 AN: 84154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103568

Other (OTH) AF: 0.00 AC: 0 AN: 59620

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D;D;D
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;.;.
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.2	M;M;M
PhyloP100		3.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.047	D;D;D
Sift4G	Benign	0.069	T;T;T
Polyphen		0.055	B;B;B
Vest4		0.86
MVP		0.63
MPC		1.2
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.72
gMVP		0.88
Mutation Taster		=52/48	polymorphism

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: rs1167877969; hg19: chr11-134253672; COSMIC: COSV100437855; COSMIC: COSV100437855;