rs10882644
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_002860.4(ALDH18A1):c.809-330G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 361,078 control chromosomes in the GnomAD database, including 17,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.27 ( 6712 hom., cov: 32)
Exomes 𝑓: 0.31 ( 10735 hom. )
Consequence
ALDH18A1
NM_002860.4 intron
NM_002860.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.362
Genes affected
ALDH18A1 (HGNC:9722): (aldehyde dehydrogenase 18 family member A1) This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 10-95628822-C-T is Benign according to our data. Variant chr10-95628822-C-T is described in ClinVar as [Benign]. Clinvar id is 683818.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH18A1 | NM_002860.4 | c.809-330G>A | intron_variant | ENST00000371224.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH18A1 | ENST00000371224.7 | c.809-330G>A | intron_variant | 1 | NM_002860.4 | P3 | |||
ALDH18A1 | ENST00000371221.3 | c.803-330G>A | intron_variant | 1 | A1 | ||||
ALDH18A1 | ENST00000489386.1 | n.32G>A | non_coding_transcript_exon_variant | 1/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.274 AC: 41626AN: 151996Hom.: 6720 Cov.: 32
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GnomAD4 exome AF: 0.305 AC: 63743AN: 208964Hom.: 10735 Cov.: 0 AF XY: 0.294 AC XY: 33255AN XY: 113276
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GnomAD4 genome ? AF: 0.274 AC: 41608AN: 152114Hom.: 6712 Cov.: 32 AF XY: 0.272 AC XY: 20224AN XY: 74344
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at