14-87993008-G-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_000153.4(GALC):c.157C>A(p.Arg53Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,626 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
Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
GALC
NM_000153.4 synonymous
NM_000153.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.66
Publications
3 publications found
Genes affected
GALC (HGNC:4115): (galactosylceramidase) This gene encodes a lysosomal protein which hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations in this gene have been associated with Krabbe disease, also known as globoid cell leukodystrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
GALC Gene-Disease associations (from GenCC):
- Krabbe diseaseInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Myriad Women’s Health, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Genomics England PanelApp
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP7
Synonymous conserved (PhyloP=2.66 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000153.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GALC | NM_000153.4 | MANE Select | c.157C>A | p.Arg53Arg | synonymous | Exon 1 of 17 | NP_000144.2 | ||
| GALC | NM_001201401.2 | c.157C>A | p.Arg53Arg | synonymous | Exon 1 of 16 | NP_001188330.1 | |||
| GALC | NR_187582.1 | n.175C>A | non_coding_transcript_exon | Exon 1 of 16 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GALC | ENST00000261304.7 | TSL:1 MANE Select | c.157C>A | p.Arg53Arg | synonymous | Exon 1 of 17 | ENSP00000261304.2 | ||
| GALC | ENST00000622264.4 | TSL:1 | c.145C>A | p.Arg49Arg | synonymous | Exon 1 of 10 | ENSP00000480649.1 | ||
| GALC | ENST00000474294.6 | TSL:1 | n.147C>A | non_coding_transcript_exon | Exon 1 of 10 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.20e-7 AC: 1AN: 1388626Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1AN XY: 687026 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1388626
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
687026
show subpopulations
African (AFR)
AF:
AC:
0
AN:
29008
American (AMR)
AF:
AC:
0
AN:
37400
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24464
East Asian (EAS)
AF:
AC:
0
AN:
34170
South Asian (SAS)
AF:
AC:
0
AN:
79032
European-Finnish (FIN)
AF:
AC:
0
AN:
39696
Middle Eastern (MID)
AF:
AC:
0
AN:
4248
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1083112
Other (OTH)
AF:
AC:
0
AN:
57496
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Galactosylceramide beta-galactosidase deficiency (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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