14-74058485-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The NM_005589.4(ALDH6A1):c.*2157C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 147,556 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 Benign (★).
Frequency
Genomes: 𝑓 0.0053 ( 1 hom., cov: 30)
Exomes 𝑓: 0.0 ( 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: -0.340
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 -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 14-74058485-G-A is Benign according to our data. Variant chr14-74058485-G-A is described in ClinVar as [Benign]. Clinvar id is 884863.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00528 (779/147556) while in subpopulation AFR AF= 0.0178 (721/40430). AF 95% confidence interval is 0.0168. There are 1 homozygotes in gnomad4. There are 359 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.*2157C>T | 3_prime_UTR_variant | 12/12 | ENST00000553458.6 | ||
BBOF1 | NM_025057.3 | c.1578+1227G>A | intron_variant | ENST00000394009.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH6A1 | ENST00000553458.6 | c.*2157C>T | 3_prime_UTR_variant | 12/12 | 1 | NM_005589.4 | P1 | ||
BBOF1 | ENST00000394009.5 | c.1578+1227G>A | intron_variant | 2 | NM_025057.3 | P1 | |||
BBOF1 | ENST00000492026.4 | n.1379+1227G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00527 AC: 777AN: 147556Hom.: 1 Cov.: 30
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 12Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 6
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GnomAD4 genome ? AF: 0.00528 AC: 779AN: 147556Hom.: 1 Cov.: 30 AF XY: 0.00501 AC XY: 359AN XY: 71682
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Methylmalonate semialdehyde dehydrogenase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
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