22-40346469-T-TCCCGC

Position:

• chr22-40346469-T-TCCCGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000623632.4(ADSL):​c.-80_-76dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,431,728 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (2 hom.)
• Consequence: ADSL ENST00000623632.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.110

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-40346469-T-TCCCGC is Benign according to our data. Variant chr22-40346469-T-TCCCGC is described in ClinVar as [Benign]. Clinvar id is 1628739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000933 (142/152240) while in subpopulation AFR AF= 0.00313 (130/41552). AF 95% confidence interval is 0.00269. There are 0 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADSL	NM_000026.4			upstream_gene_variant		ENST00000623063.3	NP_000017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADSL	ENST00000623063.3			upstream_gene_variant		1	NM_000026.4	ENSP00000485525	P1

Frequencies

GnomAD3 genomes AF: 0.000933 AC: 142 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000154 AC: 197 AN: 1279488 Hom.: 2 Cov.: 20 AF XY: 0.000194 AC XY: 122 AN XY: 630170

Gnomad4 AFR exome AF: 0.00281

Gnomad4 AMR exome AF: 0.000285

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000304

Gnomad4 OTH exome AF: 0.000223

GnomAD4 genome AF: 0.000933 AC: 142 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.000967 AC XY: 72 AN XY: 74454

Gnomad4 AFR AF: 0.00313

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.000997

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Adenylosuccinate lyase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1237603952; hg19: chr22-40742473;