rs387906314
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_003748.4(ALDH4A1):βc.21delGβ(p.Leu8SerfsTer23) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000925 in 1,481,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ).
Frequency
Consequence
NM_003748.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALDH4A1 | NM_003748.4 | c.21delG | p.Leu8SerfsTer23 | frameshift_variant | Exon 1 of 15 | ENST00000375341.8 | NP_003739.2 | |
ALDH4A1 | NM_170726.3 | c.21delG | p.Leu8SerfsTer23 | frameshift_variant | Exon 1 of 16 | NP_733844.1 | ||
ALDH4A1 | NM_001319218.2 | c.21delG | p.Leu8SerfsTer23 | frameshift_variant | Exon 1 of 14 | NP_001306147.1 | ||
LOC124903866 | XR_007065519.1 | n.140+251delC | intron_variant | Intron 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALDH4A1 | ENST00000375341.8 | c.21delG | p.Leu8SerfsTer23 | frameshift_variant | Exon 1 of 15 | 1 | NM_003748.4 | ENSP00000364490.3 | ||
ALDH4A1 | ENST00000290597.9 | c.21delG | p.Leu8SerfsTer23 | frameshift_variant | Exon 1 of 16 | 1 | ENSP00000290597.5 | |||
ALDH4A1 | ENST00000538839.5 | c.21delG | p.Leu8SerfsTer23 | frameshift_variant | Exon 1 of 14 | 1 | ENSP00000446071.1 | |||
ALDH4A1 | ENST00000432718.1 | c.21delG | p.Leu8fs | frameshift_variant | Exon 1 of 6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000100 AC: 1AN: 99934Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 55668
GnomAD4 exome AF: 0.0000948 AC: 126AN: 1329052Hom.: 0 Cov.: 30 AF XY: 0.0000855 AC XY: 56AN XY: 655174
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74308
ClinVar
Submissions by phenotype
Hyperprolinemia type 2 Pathogenic:2
The ALDH4A1 c.21delG (p.Leu8SerfsTer23) variant results in a frameshift and is predicted to cause a truncation of the protein. The p.Leu8SerfsTer23 variant has been reported in one study in which it is found in a total of two individuals with hyperprolinemia including in one in a homozygous state and in one in a compound heterozygous state with a second missense variant (Geraghty et al. 1998). Control data are unavailable for this variant, which is reported at a frequency of 0.000058 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the evidence and the potential impact of frameshift variants, the p.Leu8SerfsTer23 variant is classified as likely pathogenic for hyperprolinemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
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not provided Pathogenic:1
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 10971205, 9700195) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at