2-167869160-C-A

Variant names:

• chr2-167869160-C-A
• rs2105444552
• NM_020981.4:c.121C>A

Variant summary

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

The NM_020981.4(B3GALT1):​c.121C>A​(p.Leu41Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L41V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GALT1 NM_020981.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• Publications: 0 publications found

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:40089): (B3GALT1 antisense RNA 1)

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=0.08050403).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020981.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT1	NM_020981.4	MANE Select	c.121C>A	p.Leu41Ile	missense	Exon 5 of 5	NP_066191.1	Q9Y5Z6
	B3GALT1-AS1	NR_131227.1		n.328+580G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT1	ENST00000392690.4	TSL:6 MANE Select	c.121C>A	p.Leu41Ile	missense	Exon 5 of 5	ENSP00000376456.2	Q9Y5Z6
	B3GALT1	ENST00000970731.1		c.121C>A	p.Leu41Ile	missense	Exon 3 of 3	ENSP00000640790.1
	B3GALT1-AS1	ENST00000430546.2	TSL:3	n.362+580G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.075
Sift	Benign	0.81	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.35		Gain of methylation at K36 (P = 0.0602)
MVP		0.46
MPC		0.51
ClinPred		0.27	T
GERP RS		3.9
Varity_R		0.038
gMVP		0.45
Mutation Taster		=89/11	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: rs2105444552; hg19: chr2-168725670;