rs370707645
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_003748.4(ALDH4A1):c.1272C>T(p.Ser424Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,613,614 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 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
ALDH4A1
NM_003748.4 synonymous
NM_003748.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -10.4
Genes affected
ALDH4A1 (HGNC:406): (aldehyde dehydrogenase 4 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 1-18876381-G-A is Benign according to our data. Variant chr1-18876381-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 471327.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-10.4 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000155 (227/1461442) while in subpopulation AMR AF= 0.000447 (20/44714). AF 95% confidence interval is 0.000296. There are 0 homozygotes in gnomad4_exome. There are 112 alleles in male gnomad4_exome subpopulation. Median coverage is 42. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALDH4A1 | NM_003748.4 | c.1272C>T | p.Ser424Ser | synonymous_variant | 12/15 | ENST00000375341.8 | NP_003739.2 | |
ALDH4A1 | NM_170726.3 | c.1272C>T | p.Ser424Ser | synonymous_variant | 12/16 | NP_733844.1 | ||
ALDH4A1 | NM_001161504.2 | c.1092C>T | p.Ser364Ser | synonymous_variant | 12/15 | NP_001154976.1 | ||
ALDH4A1 | NM_001319218.2 | c.1185+827C>T | intron_variant | NP_001306147.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALDH4A1 | ENST00000375341.8 | c.1272C>T | p.Ser424Ser | synonymous_variant | 12/15 | 1 | NM_003748.4 | ENSP00000364490.3 | ||
ALDH4A1 | ENST00000290597.9 | c.1272C>T | p.Ser424Ser | synonymous_variant | 12/16 | 1 | ENSP00000290597.5 | |||
ALDH4A1 | ENST00000538839.5 | c.1185+827C>T | intron_variant | 1 | ENSP00000446071.1 | |||||
ALDH4A1 | ENST00000538309.5 | c.1092C>T | p.Ser364Ser | synonymous_variant | 12/15 | 2 | ENSP00000442988.1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000163 AC: 41AN: 250860Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135618
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GnomAD4 exome AF: 0.000155 AC: 227AN: 1461442Hom.: 0 Cov.: 42 AF XY: 0.000154 AC XY: 112AN XY: 727026
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74344
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hyperprolinemia type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 15, 2021 | - - |
Computational scores
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Name
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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