12-57628835-C-A

Position:

• chr12-57628835-C-A

Variant summary

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

The NM_001478.5(B4GALNT1):​c.880G>T​(p.Ala294Ser) 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. 15/23 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. A294T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: B4GALNT1 NM_001478.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

Genes affected

B4GALNT1 (HGNC:4117): (beta-1,4-N-acetyl-galactosaminyltransferase 1) GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

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	UniProt
B4GALNT1	NM_001478.5	c.880G>T	p.Ala294Ser	missense_variant	8/11	ENST00000341156.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALNT1	ENST00000341156.9	c.880G>T	p.Ala294Ser	missense_variant	8/11	1	NM_001478.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.21	T;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.12	N;N;.
REVEL	Benign	0.024
Sift	Benign	0.80	T;T;.
Sift4G	Benign	0.74	T;T;T
Polyphen		0.026	B;.;B
Vest4		0.20
MutPred		0.39		Gain of phosphorylation at A294 (P = 0.0346);.;.;
MVP		0.45
MPC		0.19
ClinPred		0.31	T
GERP RS		-2.7
Varity_R		0.042
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.47		Position offset: -14

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs147301375; hg19: chr12-58022618;