11-134384144-G-T

Variant names:

• chr11-134384144-G-T
• rs150624857
• NM_054025.3:c.157C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_054025.3(B3GAT1):​c.157C>A​(p.Pro53Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. P53A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: B3GAT1 NM_054025.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11850795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GAT1	NM_054025.3	c.157C>A	p.Pro53Thr	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.157C>A	p.Pro53Thr	missense_variant	Exon 3 of 6	1	NM_054025.3	ENSP00000307875.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414318 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 697422

African (AFR) AF: 0.00 AC: 0 AN: 32878

American (AMR) AF: 0.00 AC: 0 AN: 43264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24428

East Asian (EAS) AF: 0.00 AC: 0 AN: 38940

South Asian (SAS) AF: 0.00 AC: 0 AN: 82364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5530

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1087878

Other (OTH) AF: 0.00 AC: 0 AN: 58532

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;.;.
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L
PhyloP100		1.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.15	N;N;N
REVEL	Benign	0.097
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.032	B;B;B
Vest4		0.31
MVP		0.12
MPC		0.97
ClinPred		0.38	T
GERP RS		3.6
Varity_R		0.085
gMVP		0.70
Mutation Taster		=80/20	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: rs150624857; hg19: chr11-134254038;