chr9-91214085-GTAAA-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001698.3(AUH):c.*259_*262del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 380,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
AUH
NM_001698.3 3_prime_UTR
NM_001698.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.35
Genes affected
AUH (HGNC:890): (AU RNA binding methylglutaconyl-CoA hydratase) This gene encodes bifunctional mitochondrial protein that has both RNA-binding and hydratase activities. The encoded protein is a methylglutaconyl-CoA hydratase that catalyzes the hydration of 3-methylglutaconyl-CoA to 3-hydroxy-3-methyl-glutaryl-CoA, a critical step in the leucine degradation pathway. This protein also binds AU-rich elements (AREs) found in the 3' UTRs of rapidly decaying mRNAs including c-fos, c-myc and granulocyte/ macrophage colony stimulating factor. ARE elements are involved in directing RNA to rapid degradation and deadenylation. This protein is localizes to the mitochondrial matrix and the inner mitochondrial membrane and may be involved in mitochondrial protein synthesis. Mutations in this gene are the cause of 3-methylglutaconic aciduria, type I. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AUH | NM_001698.3 | c.*259_*262del | 3_prime_UTR_variant | 10/10 | ENST00000375731.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AUH | ENST00000375731.9 | c.*259_*262del | 3_prime_UTR_variant | 10/10 | 1 | NM_001698.3 | P1 | ||
AUH | ENST00000303617.5 | c.*259_*262del | 3_prime_UTR_variant | 9/9 | 1 | ||||
AUH | ENST00000473695.1 | n.503_506del | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152190Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000114 AC: 26AN: 228244Hom.: 0 AF XY: 0.0000993 AC XY: 12AN XY: 120824
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74488
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
3-methylglutaconic aciduria type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at