rs534200134

Variant names:

• chr12-57631912-C-G
• rs534200134
• NM_001478.5:c.218+3G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-57631912-C-G
• chr12-57631912-C-T

Variant summary

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

The NM_001413967.1(B4GALNT1):​c.218+3G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000008 in 1,250,402 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: B4GALNT1 NM_001413967.1 splice_region, intron
• Scores: Splicing: ADA: 0.9785
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701
• Publications: 0 publications found

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]

B4GALNT1 Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 26

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413967.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT1	NM_001478.5	MANE Select	c.218+3G>C		splice_region intron	N/A	NP_001469.1
	B4GALNT1	NM_001413967.1		c.218+3G>C		splice_region intron	N/A	NP_001400896.1
	B4GALNT1	NM_001413968.1		c.218+3G>C		splice_region intron	N/A	NP_001400897.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.218+3G>C		splice_region intron	N/A	ENSP00000341562.4
	B4GALNT1	ENST00000550764.5	TSL:1	c.218+3G>C		splice_region intron	N/A	ENSP00000450303.1
	B4GALNT1	ENST00000882412.1		c.218+3G>C		splice_region intron	N/A	ENSP00000552471.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.00e-7 AC: 1 AN: 1250402 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 602352

African (AFR) AF: 0.00 AC: 0 AN: 25376

American (AMR) AF: 0.00 AC: 0 AN: 16084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17650

East Asian (EAS) AF: 0.00 AC: 0 AN: 31290

South Asian (SAS) AF: 0.00 AC: 0 AN: 49812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4048

European-Non Finnish (NFE) AF: 9.90e-7 AC: 1 AN: 1010206

Other (OTH) AF: 0.00 AC: 0 AN: 51412

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Benign	0.62
PhyloP100		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 29

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

Other links and lift over

dbSNP: rs534200134; hg19: chr12-58025695;