12-553194-G-T

Variant names:

• chr12-553194-G-T
• rs370295905
• NM_173593.4:c.1271G>T

Variant summary

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

The NM_173593.4(B4GALNT3):​c.1271G>T​(p.Gly424Val) variant causes a missense, splice region 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. 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. G424D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: B4GALNT3 NM_173593.4 missense, splice_region
• Scores: Splicing: ADA: 0.9991
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.992
• Publications: 0 publications found

Genes affected

B4GALNT3 (HGNC:24137): (beta-1,4-N-acetyl-galactosaminyltransferase 3) B4GALNT3 transfers N-acetylgalactosamine (GalNAc) onto glucosyl residues to form N,N-prime-diacetyllactosediamine (LacdiNAc, or LDN), a unique terminal structure of cell surface N-glycans (Ikehara et al., 2006 [PubMed 16728562]).[supplied by OMIM, Aug 2008]

ENSG00000304192 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT3	NM_173593.4	c.1271G>T	p.Gly424Val	missense_variant, splice_region_variant	Exon 14 of 20	ENST00000266383.10	NP_775864.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT3	ENST00000266383.10	c.1271G>T	p.Gly424Val	missense_variant, splice_region_variant	Exon 14 of 20	1	NM_173593.4	ENSP00000266383.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0072	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.
PhyloP100		0.99
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.14
Sift	Benign	0.050	D;D
Sift4G	Benign	0.31	T;T
Polyphen		0.96	D;D
Vest4		0.29
MutPred		0.21		Gain of loop (P = 0.024);.;
MVP		0.48
MPC		0.58
ClinPred		0.92	D
GERP RS		5.2
Varity_R		0.25
gMVP		0.59
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: -44
DS_AL_spliceai		0.37		Position offset: 0

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

Other links and lift over

dbSNP: rs370295905; hg19: chr12-662360;