4-1002460-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The NM_000203.5: c.1164G>C (p.Thr388=) variant is a synonymous (silent) variant. The highest population minor allele frequency in gnomAD v4.1.0 is 0.2976 (25114/84382 alleles; 3978 homozygotes; Grpmax Filtering AF 95% confidence = 0.2945) in the South Asian population, which is higher than the ClinGen Lysosomal Diseases VCEP’s threshold for BA1 (>0.005), and therefore meets this criterion (BA1). There is a ClinVar entry for this variant (Variation ID: 92625). In summary, this variant meets the criteria to be classified as benign for MPS I based on the ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 1.0.0): BA1.(Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on December 6, 2024) LINK:https://erepo.genome.network/evrepo/ui/classification/CA145867/MONDO:0001586/091
Frequency
Consequence
NM_000203.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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IDUA | ENST00000514224.2 | c.1164G>C | p.Thr388Thr | synonymous_variant | Exon 8 of 14 | 2 | NM_000203.5 | ENSP00000425081.2 | ||
IDUA | ENST00000247933.9 | c.1164G>C | p.Thr388Thr | synonymous_variant | Exon 8 of 14 | 1 | ENSP00000247933.4 | |||
IDUA | ENST00000514698.5 | n.1271G>C | non_coding_transcript_exon_variant | Exon 5 of 11 | 5 | |||||
IDUA | ENST00000652070.1 | n.1220G>C | non_coding_transcript_exon_variant | Exon 7 of 13 |
Frequencies
GnomAD3 genomes AF: 0.173 AC: 26241AN: 152064Hom.: 2372 Cov.: 34
GnomAD3 exomes AF: 0.174 AC: 26448AN: 151750Hom.: 2720 AF XY: 0.185 AC XY: 15043AN XY: 81426
GnomAD4 exome AF: 0.161 AC: 225509AN: 1398620Hom.: 19662 Cov.: 35 AF XY: 0.165 AC XY: 113950AN XY: 690122
GnomAD4 genome AF: 0.172 AC: 26238AN: 152180Hom.: 2368 Cov.: 34 AF XY: 0.173 AC XY: 12844AN XY: 74382
ClinVar
Submissions by phenotype
not specified Benign:5
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Mucopolysaccharidosis type 1 Benign:4
The NM_000203.5: c.1164G>C (p.Thr388=) variant is a synonymous (silent) variant. The highest population minor allele frequency in gnomAD v4.1.0 is 0.2976 (25114/84382 alleles; 3978 homozygotes; Grpmax Filtering AF 95% confidence = 0.2945) in the South Asian population, which is higher than the ClinGen Lysosomal Diseases VCEP’s threshold for BA1 (>0.005), and therefore meets this criterion (BA1). There is a ClinVar entry for this variant (Variation ID: 92625). In summary, this variant meets the criteria to be classified as benign for MPS I based on the ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 1.0.0): BA1. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on December 6, 2024) -
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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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not provided Benign:4
This variant is associated with the following publications: (PMID: 16438163, 28649516, 9391892, 12509712) -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at