rs56194647
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000153.4(GALC):āc.397T>Cā(p.Leu133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 1,613,542 control chromosomes in the GnomAD database, including 280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.024 ( 153 hom., cov: 32)
Exomes š: 0.0026 ( 127 hom. )
Consequence
GALC
NM_000153.4 synonymous
NM_000153.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.75
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
?
Variant 14-87986534-A-G is Benign according to our data. Variant chr14-87986534-A-G is described in ClinVar as [Benign]. Clinvar id is 255376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-87986534-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.75 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALC | NM_000153.4 | c.397T>C | p.Leu133= | synonymous_variant | 4/17 | ENST00000261304.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALC | ENST00000261304.7 | c.397T>C | p.Leu133= | synonymous_variant | 4/17 | 1 | NM_000153.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0236 AC: 3593AN: 152118Hom.: 154 Cov.: 32
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GnomAD3 exomes AF: 0.00635 AC: 1583AN: 249412Hom.: 51 AF XY: 0.00464 AC XY: 628AN XY: 135312
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GnomAD4 exome AF: 0.00263 AC: 3841AN: 1461306Hom.: 127 Cov.: 30 AF XY: 0.00224 AC XY: 1629AN XY: 727000
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GnomAD4 genome ? AF: 0.0237 AC: 3608AN: 152236Hom.: 153 Cov.: 32 AF XY: 0.0221 AC XY: 1647AN XY: 74446
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Galactosylceramide beta-galactosidase deficiency Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 13, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 31, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 01, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at