rs112531377
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000153.4(GALC):c.1236T>A(p.Val412=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,598,008 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 0 hom. )
Consequence
GALC
NM_000153.4 synonymous
NM_000153.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.838
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 14-87950674-A-T is Benign according to our data. Variant chr14-87950674-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 456713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.838 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALC | NM_000153.4 | c.1236T>A | p.Val412= | synonymous_variant | 11/17 | ENST00000261304.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALC | ENST00000261304.7 | c.1236T>A | p.Val412= | synonymous_variant | 11/17 | 1 | NM_000153.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00289 AC: 439AN: 151928Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000753 AC: 187AN: 248434Hom.: 0 AF XY: 0.000534 AC XY: 72AN XY: 134836
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GnomAD4 exome AF: 0.000292 AC: 422AN: 1445962Hom.: 0 Cov.: 27 AF XY: 0.000268 AC XY: 193AN XY: 720234
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GnomAD4 genome ? AF: 0.00294 AC: 447AN: 152046Hom.: 1 Cov.: 32 AF XY: 0.00312 AC XY: 232AN XY: 74328
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Galactosylceramide beta-galactosidase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
GALC-related condition Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 12, 2019 | 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). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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