14-87934720-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000153.4(GALC):c.*12G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000153.4 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GALC | NM_000153.4 | c.*12G>A | 3_prime_UTR_variant | Exon 17 of 17 | ENST00000261304.7 | NP_000144.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152022Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248824Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135004
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460792Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726706
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152022Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74252
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: GALC c.*12G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 4e-06 in 248824 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.*12G>A has been reported in the literature in an infant that had low GALC activity in dried blood spot test (Orsini_2016). This report does not provide unequivocal conclusions about association of the variant with Krabbe Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Galactosylceramide beta-galactosidase deficiency Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at