rs421466
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000153.4(GALC):c.1698A>T(p.Val566=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,588,716 control chromosomes in the GnomAD database, including 780,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V566V) has been classified as Likely benign.
Frequency
Consequence
NM_000153.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALC | NM_000153.4 | c.1698A>T | p.Val566= | synonymous_variant | 15/17 | ENST00000261304.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALC | ENST00000261304.7 | c.1698A>T | p.Val566= | synonymous_variant | 15/17 | 1 | NM_000153.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.957 AC: 145443AN: 151930Hom.: 69914 Cov.: 33
GnomAD3 exomes AF: 0.985 AC: 244906AN: 248700Hom.: 120738 AF XY: 0.988 AC XY: 133296AN XY: 134920
GnomAD4 exome AF: 0.994 AC: 1427972AN: 1436668Hom.: 710085 Cov.: 32 AF XY: 0.995 AC XY: 712611AN XY: 716452
GnomAD4 genome ? AF: 0.957 AC: 145543AN: 152048Hom.: 69954 Cov.: 33 AF XY: 0.958 AC XY: 71209AN XY: 74316
ClinVar
Submissions by phenotype
Galactosylceramide beta-galactosidase deficiency Benign:5
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 16, 2016 | Variant summary: The GALC c.1698A>T (p.Val566Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SQp55. This variant was found in 118550/120624 control chromosomes (58347 homozygotes) at a frequency of 0.9828061, which is approximately 440 times the estimated maximal expected allele frequency of a pathogenic GALC variant (0.0022361), suggesting this variant is a benign polymorphism. The variant has been found to co-occur in Krabbe Disease patients with compound heterozygous pathogenic variants that would explain the patients phenotype. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign. - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 19, 2015 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 27, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
GALC-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 21, 2021 | 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