rs1329070853
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_000048.4(ASL):c.1045_1062+7del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. G348G) has been classified as Likely benign.
Frequency
Consequence
NM_000048.4 splice_donor, splice_donor_5th_base, coding_sequence, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASL | NM_000048.4 | c.1045_1062+7del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 14/17 | ENST00000304874.14 | ||
ASL | NM_001024943.2 | c.1045_1062+7del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 13/16 | |||
ASL | NM_001024944.2 | c.985_1002+7del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 12/15 | |||
ASL | NM_001024946.2 | c.967_984+7del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASL | ENST00000304874.14 | c.1045_1062+7del | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 14/17 | 1 | NM_000048.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461302Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726964
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Argininosuccinate lyase deficiency Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This variant results in the deletion of part of exon 14 (c.1045_1062+7del) of the ASL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ASL are known to be pathogenic (PMID: 2263616, 24166829). This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with argininosuccinate lyase deficiency (PMID: 16941645; Invitae). ClinVar contains an entry for this variant (Variation ID: 529426). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at