rs398607
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000153.4(GALC):āc.1685T>Cā(p.Ile562Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,576,428 control chromosomes in the GnomAD database, including 174,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,other (ā ā ).
Frequency
Consequence
NM_000153.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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GALC | NM_000153.4 | c.1685T>C | p.Ile562Thr | missense_variant | Exon 15 of 17 | ENST00000261304.7 | NP_000144.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.492 AC: 74706AN: 151734Hom.: 19079 Cov.: 32
GnomAD3 exomes AF: 0.433 AC: 107634AN: 248542Hom.: 24679 AF XY: 0.435 AC XY: 58669AN XY: 134844
GnomAD4 exome AF: 0.462 AC: 658766AN: 1424576Hom.: 155737 Cov.: 30 AF XY: 0.462 AC XY: 328556AN XY: 711174
GnomAD4 genome AF: 0.493 AC: 74789AN: 151852Hom.: 19109 Cov.: 32 AF XY: 0.488 AC XY: 36174AN XY: 74186
ClinVar
Submissions by phenotype
Galactosylceramide beta-galactosidase deficiency Benign:5Other:3
- pseudodeficiency allele
Variant interpreted as Benign and reported on 11-13-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -
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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. -
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The p.Ile562Thr variant in GALC has been identified in 1 Japanese individual with Krabbe disease (PMID: 24252386). This variant is classified as benign for autosomal recessive Krabbe disease because it has been identified in >60% of African chromosomes by ExAC (http://gnomad.broadinstitute.org/). -
not specified Benign:4
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not provided Benign:2Other:2
Variant identified in multiple GenomeConnect participants. Variant classified as Benign (pseudodeficiency allele) and reported, most recently, on 06-18-2021 by Lab or GTR ID 500031. Variant also classified as Benign and reported on 09-16-2019 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
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This variant is associated with the following publications: (PMID: 32661301, 27126738, 26865610, 27535533, 24078576, 26795590, 24252386) -
Variant reported in multiple GenomeConnect participants by mulitple clinical testing laboratories. Variant classified as other/Benign by all laboratories and reported most recently on 05-11-2022 by Variantxy and on 01-25-2022 by Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at