rs8135371
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000026.4(ADSL):c.793-49A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,559,676 control chromosomes in the GnomAD database, including 16,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.13 ( 1398 hom., cov: 32)
Exomes 𝑓: 0.14 ( 14845 hom. )
Consequence
ADSL
NM_000026.4 intron
NM_000026.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.16
Genes affected
ADSL (HGNC:291): (adenylosuccinate lyase) The protein encoded by this gene belongs to the lyase 1 family. It is an essential enzyme involved in purine metabolism, and catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (S-AMP) to adenosine monophosphate (AMP). Mutations in this gene are associated with adenylosuccinase deficiency (ADSLD), a disorder marked with psychomotor retardation, epilepsy or autistic features. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
Variant 22-40361224-A-C is Benign according to our data. Variant chr22-40361224-A-C is described in ClinVar as [Benign]. Clinvar id is 670882.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADSL | NM_000026.4 | c.793-49A>C | intron_variant | ENST00000623063.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADSL | ENST00000623063.3 | c.793-49A>C | intron_variant | 1 | NM_000026.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.130 AC: 19742AN: 151924Hom.: 1390 Cov.: 32
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GnomAD3 exomes AF: 0.134 AC: 33625AN: 251178Hom.: 2612 AF XY: 0.140 AC XY: 18970AN XY: 135776
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GnomAD4 exome AF: 0.141 AC: 199149AN: 1407634Hom.: 14845 Cov.: 25 AF XY: 0.144 AC XY: 101038AN XY: 703538
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GnomAD4 genome ? AF: 0.130 AC: 19768AN: 152042Hom.: 1398 Cov.: 32 AF XY: 0.134 AC XY: 9966AN XY: 74310
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
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