chr22-40346524-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000026.4(ADSL):c.-35G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 1,587,726 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 Uncertain significance (★).
Frequency
Consequence
NM_000026.4 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADSL | ENST00000623063 | c.-35G>A | 5_prime_UTR_variant | Exon 1 of 13 | 1 | NM_000026.4 | ENSP00000485525.1 | |||
ENSG00000284431 | ENST00000639722.1 | n.-35G>A | upstream_gene_variant | 5 | ENSP00000492828.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152232Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000142 AC: 3AN: 211402Hom.: 0 AF XY: 0.00000867 AC XY: 1AN XY: 115318
GnomAD4 exome AF: 0.00000348 AC: 5AN: 1435376Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 2AN XY: 712756
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152350Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74506
ClinVar
Submissions by phenotype
not provided Uncertain:1
c.-35 G>A in exon 1 of the ADSL gene (NM_000026.2) The c.-35 G>A sequence change in the 5' untranslated region of the ADSL gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.-35 G>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although this variant is not expected to alter the ATG initiation codon or Kozak sequence, other regulatory mutations have been reported in the ADSL gene in association with ADSL deficiency. However, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at