Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001478.5(B4GALNT1):c.358C>T(p.Gln120*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
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
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-57631225-G-A is Pathogenic according to our data. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-57631225-G-A is described in CliVar as Pathogenic. Clinvar id is 60526.Status of the report is criteria_provided_single_submitter, 1 stars.
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29747824, 28709807, 23746551, 25141825, 30521973) -