rs6831280
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000203.5(IDUA):c.1081G>A(p.Ala361Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,611,054 control chromosomes in the GnomAD database, including 22,735 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A361P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000203.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDUA | NM_000203.5 | c.1081G>A | p.Ala361Thr | missense_variant | 8/14 | ENST00000514224.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDUA | ENST00000514224.2 | c.1081G>A | p.Ala361Thr | missense_variant | 8/14 | 2 | NM_000203.5 | P1 | |
IDUA | ENST00000247933.9 | c.1081G>A | p.Ala361Thr | missense_variant | 8/14 | 1 | P1 | ||
IDUA | ENST00000514698.5 | n.1188G>A | non_coding_transcript_exon_variant | 5/11 | 5 | ||||
IDUA | ENST00000652070.1 | n.1137G>A | non_coding_transcript_exon_variant | 7/13 |
Frequencies
GnomAD3 genomes AF: 0.172 AC: 26116AN: 152110Hom.: 2344 Cov.: 34
GnomAD3 exomes AF: 0.172 AC: 41988AN: 243470Hom.: 4099 AF XY: 0.181 AC XY: 23973AN XY: 132448
GnomAD4 exome AF: 0.161 AC: 234399AN: 1458830Hom.: 20394 Cov.: 35 AF XY: 0.165 AC XY: 119589AN XY: 725586
GnomAD4 genome AF: 0.172 AC: 26114AN: 152224Hom.: 2341 Cov.: 34 AF XY: 0.172 AC XY: 12793AN XY: 74430
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 02, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Mucopolysaccharidosis type 1 Benign:3Other:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 29, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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 provided, no classification provided | literature only | GeneReviews | - | Pseudodeficiency variants - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 29, 2018 | This variant is associated with the following publications: (PMID: 28649516, 29801497, 26256109, 27884173, 24875751) - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 29, 2016 | - - |
Hurler syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | May 18, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at