rs17001863

chr22-40363304-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000026.4(ADSL):c.1101+233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,226 control chromosomes in the GnomAD database, including 1,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1221 hom., cov: 32)
• Consequence: ADSL NM_000026.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-40363304-A-G is Benign according to our data. Variant chr22-40363304-A-G is described in ClinVar as [Benign]. Clinvar id is 678102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADSL	NM_000026.4	c.1101+233A>G		intron_variant		ENST00000623063.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADSL	ENST00000623063.3	c.1101+233A>G		intron_variant		1	NM_000026.4	P1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18407 AN: 152106 Hom.: 1214 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 18429 AN: 152226 Hom.: 1221 Cov.: 32 AF XY: 0.124 AC XY: 9239 AN XY: 74424

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0703

Gnomad4 ASJ AF: 0.0899

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.110

Alfa AF: 0.120 Hom.: 522

Bravo AF: 0.108

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 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

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17001863; hg19: chr22-40759308;