rs398122382
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001478.5(B4GALNT1):c.682C>T(p.Arg228Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R228R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001478.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
B4GALNT1 | NM_001478.5 | c.682C>T | p.Arg228Ter | stop_gained | 6/11 | ENST00000341156.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
B4GALNT1 | ENST00000341156.9 | c.682C>T | p.Arg228Ter | stop_gained | 6/11 | 1 | NM_001478.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251410Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135886
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727226
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 26 Pathogenic:4
Pathogenic, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Nov 15, 2018 | The homozygous p.Arg228Ter variant in B4GALNT1 was identified by our study in one individual with Spastic Paraplegia. This variant has been reported as homozygous in the literature in two affected family members (Boukhris et al. 2013; PMID: 23746551). This variant has been identified in <0.01% (1/33582) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs398122382). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Loss of function of the B4GALNT1 gene is an established disease mechanism in autosomal recessive Spastic Paraplegia, and this is a loss of function variant. In summary, this variant is pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 11, 2013 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Paris Brain Institute, Inserm - ICM | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Oct 18, 2021 | ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 supporting, PM2 moderate, PM3 moderate, PP1 strong - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at