rs1555383687
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_000153.4(GALC):c.411_413del(p.Lys139del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A137A) has been classified as Likely benign.
Frequency
Consequence
NM_000153.4 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALC | NM_000153.4 | c.411_413del | p.Lys139del | inframe_deletion | 4/17 | ENST00000261304.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALC | ENST00000261304.7 | c.411_413del | p.Lys139del | inframe_deletion | 4/17 | 1 | NM_000153.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458380Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 725854
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Galactosylceramide beta-galactosidase deficiency Pathogenic:2Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ege University Pediatric Genetics, Ege University | May 15, 2019 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 30, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | This variant, c.411_413del, results in the deletion of 1 amino acid(s) of the GALC protein (p.Lys139del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Krabbe disease (PMID: 23197103, 26108647, 35286032). This variant is also known as K123del. ClinVar contains an entry for this variant (Variation ID: 555281). 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