3-161086693-C-A

Position:

• chr3-161086693-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003781.4(B3GALNT1):​c.62G>T​(p.Ser21Ile) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: B3GALNT1 NM_003781.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

Genes affected

B3GALNT1 (HGNC:918): (beta-1,3-N-acetylgalactosaminyltransferase 1 (Globoside blood group)) 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). The encoded protein of this gene does not use N-acetylglucosamine as an acceptor sugar at all. [provided by RefSeq, Mar 2017]

B3GALNT1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1834186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALNT1	NM_003781.4	c.62G>T	p.Ser21Ile	missense_variant	5/5	ENST00000320474.10	NP_003772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALNT1	ENST00000320474.10	c.62G>T	p.Ser21Ile	missense_variant	5/5	1	NM_003781.4	ENSP00000323479.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251040 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135722

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Oct 04, 2022

The c.62G>T (p.S21I) alteration is located in exon 5 (coding exon 1) of the B3GALNT1 gene. This alteration results from a G to T substitution at nucleotide position 62, causing the serine (S) at amino acid position 21 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;T;T;.;T;T;T;.;.;.;.;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.77	.;.;.;.;T;T;T;T;T;T;.;T;.
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N;.;N;.;.;.;.;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.81	N;N;N;N;D;N;N;N;D;D;D;D;N
REVEL	Benign	0.15
Sift	Benign	0.16	T;T;T;T;D;T;T;T;D;D;.;.;D
Sift4G	Benign	0.16	T;T;T;T;D;T;T;.;.;D;.;.;.
Polyphen		0.0010	B;B;B;B;B;B;.;.;.;.;.;.;.
Vest4		0.20
MutPred		0.50		Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);Loss of disorder (P = 0.0495);.;
MVP		0.47
MPC		0.75
ClinPred		0.30	T
GERP RS		2.6
Varity_R		0.062

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

LitVar

Other links and lift over

dbSNP: rs767350162; hg19: chr3-160804481;