12-539071-T-C

Variant names:

• chr12-539071-T-C
• rs2302408
• NM_173593.4:c.351+2776T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173593.4(B4GALNT3):​c.351+2776T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,216 control chromosomes in the GnomAD database, including 1,123 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1123 hom., cov: 32)
• Consequence: B4GALNT3 NM_173593.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT3	NM_173593.4	c.351+2776T>C		intron_variant	Intron 3 of 19	ENST00000266383.10	NP_775864.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT3	ENST00000266383.10	c.351+2776T>C		intron_variant	Intron 3 of 19	1	NM_173593.4	ENSP00000266383.5
B4GALNT3	ENST00000535680.5	n.258+2776T>C		intron_variant	Intron 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17155 AN: 152098 Hom.: 1123 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0904

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17178 AN: 152216 Hom.: 1123 Cov.: 32 AF XY: 0.112 AC XY: 8356 AN XY: 74440

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.0945

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0782

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0859 Hom.: 296

Bravo AF: 0.115

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.77

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: rs2302408; hg19: chr12-648237;