2-167869285-C-G

Position:

• chr2-167869285-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020981.4(B3GALT1):​c.246C>G​(p.Ile82Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GALT1 NM_020981.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

Genes affected

B3GALT1 (HGNC:916): (beta-1,3-galactosyltransferase 1) This gene is a member of the beta-1,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). The beta3GalT genes are distantly related to the Drosophila Brainiac gene and have the protein coding sequence contained in a single exon. The beta3GalT proteins also contain conserved sequences not found in the beta4GalT or alpha3GalT proteins. The carbohydrate chains synthesized by these enzymes are designated as type 1, whereas beta4GalT enzymes synthesize type 2 carbohydrate chains. The ratio of type 1:type 2 chains changes during embryogenesis. By sequence similarity, the beta3GalT genes fall into at least two groups: beta3GalT4 and 4 other beta3GalT genes (beta3GalT1-3, beta3GalT5). This gene is expressed exclusively in the brain. The encoded protein shows strict donor substrate specificity for UDP-galactose. [provided by RefSeq, Jul 2008]

B3GALT1-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALT1	NM_020981.4	c.246C>G	p.Ile82Met	missense_variant	5/5	ENST00000392690.4	NP_066191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALT1	ENST00000392690.4	c.246C>G	p.Ile82Met	missense_variant	5/5	6	NM_020981.4	ENSP00000376456.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2024

The c.246C>G (p.I82M) alteration is located in exon 2 (coding exon 1) of the B3GALT1 gene. This alteration results from a C to G substitution at nucleotide position 246, causing the isoleucine (I) at amino acid position 82 to be replaced by a methionine (M). 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	Benign	0.21
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.033
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.17
Sift	Benign	0.21	T
Sift4G	Uncertain	0.023	D
Polyphen		0.82	P
Vest4		0.65
MutPred		0.54		Gain of phosphorylation at T87 (P = 0.1036);
MVP		0.62
MPC		0.49
ClinPred		0.25	T
GERP RS		3.1
Varity_R		0.10
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-168725795;