rs761573002
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001698.3(AUH):c.795C>T(p.Asp265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000096 ( 1 hom. )
Consequence
AUH
NM_001698.3 synonymous
NM_001698.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.524
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 Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 9-91220853-G-A is Benign according to our data. Variant chr9-91220853-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.524 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AUH | NM_001698.3 | c.795C>T | p.Asp265= | synonymous_variant | 7/10 | ENST00000375731.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AUH | ENST00000375731.9 | c.795C>T | p.Asp265= | synonymous_variant | 7/10 | 1 | NM_001698.3 | P1 | |
AUH | ENST00000303617.5 | c.708C>T | p.Asp236= | synonymous_variant | 6/9 | 1 | |||
AUH | ENST00000473695.1 | n.67C>T | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000103 AC: 26AN: 251426Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135882
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GnomAD4 exome AF: 0.0000958 AC: 140AN: 1461878Hom.: 1 Cov.: 31 AF XY: 0.0000963 AC XY: 70AN XY: 727242
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74364
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | AUH: BP4, BP7 - |
3-methylglutaconic aciduria type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at