rs1057516469
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000153.4(GALC):βc.1012delβ(p.Glu338AsnfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. E338E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000153.4 frameshift
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 |
---|---|---|---|---|---|---|---|
GALC | NM_000153.4 | c.1012del | p.Glu338AsnfsTer21 | frameshift_variant | 9/17 | ENST00000261304.7 | |
LOC124903355 | XR_007064295.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALC | ENST00000261304.7 | c.1012del | p.Glu338AsnfsTer21 | frameshift_variant | 9/17 | 1 | NM_000153.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249056Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135108
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461328Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726968
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Galactosylceramide beta-galactosidase deficiency Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Feb 04, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | This sequence change creates a premature translational stop signal (p.Glu338Asnfs*21) in the GALC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Krabbe disease (PMID: 9338580). This variant is also known as 964delG. ClinVar contains an entry for this variant (Variation ID: 370416). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at