ADSL p.Leu42Leu

Variant names:

• chr22-40346681-G-G
• ENST00000623063.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr22-40346682--
• chr22-40346682-C-T
• chr22-40346684-G-T
• chr22-40346684-G-C
• chr22-40346684-G-A
• chr22-40346682-CTG-TTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000623063.3(ADSL):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADSL ENST00000623063.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87
• Publications: 0 publications found

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]

ADSL Gene-Disease associations (from GenCC):

• adenylosuccinate lyase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ENSG00000284431 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000623063.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADSL	ENST00000623063.3	TSL:1 MANE Select	c.		exon_region	Exon 1 of 13	ENSP00000485525.1	P30566-1
	ADSL	ENST00000342312.9	TSL:1	c.		exon_region	Exon 1 of 12	ENSP00000341429.6	P30566-2
	ADSL	ENST00000480775.3	TSL:1	n.		exon_region	Exon 1 of 13	ENSP00000485462.2	A0A096LP92

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-40742685;