14-74058822-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_005589.4(ALDH6A1):c.*1820G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 152,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.026 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ALDH6A1
NM_005589.4 3_prime_UTR
NM_005589.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.650
Genes affected
ALDH6A1 (HGNC:7179): (aldehyde dehydrogenase 6 family member A1) This gene encodes a member of the aldehyde dehydrogenase protein family. The encoded protein is a mitochondrial methylmalonate semialdehyde dehydrogenase that plays a role in the valine and pyrimidine catabolic pathways. This protein catalyzes the irreversible oxidative decarboxylation of malonate and methylmalonate semialdehydes to acetyl- and propionyl-CoA. Methylmalonate semialdehyde dehydrogenase deficiency is characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
Variant 14-74058822-C-T is Benign according to our data. Variant chr14-74058822-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 885789.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00203 (309/152054) while in subpopulation AFR AF= 0.00685 (284/41486). AF 95% confidence interval is 0.00619. There are 0 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH6A1 | NM_005589.4 | c.*1820G>A | 3_prime_UTR_variant | 12/12 | ENST00000553458.6 | ||
BBOF1 | NM_025057.3 | c.1578+1564C>T | intron_variant | ENST00000394009.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH6A1 | ENST00000553458.6 | c.*1820G>A | 3_prime_UTR_variant | 12/12 | 1 | NM_005589.4 | P1 | ||
BBOF1 | ENST00000394009.5 | c.1578+1564C>T | intron_variant | 2 | NM_025057.3 | P1 | |||
BBOF1 | ENST00000492026.4 | n.1379+1564C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00202 AC: 307AN: 151936Hom.: 0 Cov.: 30
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0258 AC: 14AN: 542Hom.: 0 Cov.: 0 AF XY: 0.0199 AC XY: 7AN XY: 352
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Methylmalonate semialdehyde dehydrogenase deficiency Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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