14-87947814-G-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000153.4(GALC):āc.1403C>Gā(p.Thr468Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,612,742 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000153.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GALC | NM_000153.4 | c.1403C>G | p.Thr468Ser | missense_variant | Exon 13 of 17 | ENST00000261304.7 | NP_000144.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00439 AC: 667AN: 152050Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.00110 AC: 273AN: 248876Hom.: 1 AF XY: 0.000763 AC XY: 103AN XY: 135014
GnomAD4 exome AF: 0.000469 AC: 685AN: 1460574Hom.: 2 Cov.: 31 AF XY: 0.000398 AC XY: 289AN XY: 726648
GnomAD4 genome AF: 0.00446 AC: 678AN: 152168Hom.: 4 Cov.: 32 AF XY: 0.00444 AC XY: 330AN XY: 74404
ClinVar
Submissions by phenotype
Galactosylceramide beta-galactosidase deficiency Uncertain:1Benign:3
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This variant is interpreted as a Uncertain Significance - Conflicting Evidence, for Krabbe disease, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. BS1 => Allele frequency is greater than expected for disorder. BS2-Supporting => BS2 downgraded in strength to supporting. -
not provided Benign:3
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This variant is associated with the following publications: (PMID: 32019516, 27638593, 9338580, 21228398, 20981092, 22995991) -
GALC: BS1 -
not specified Benign:1
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GALC-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at