7-66081579-CA-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000048.4(ASL):c.13-209del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ASL NM_000048.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.581

Genes affected

ASL (HGNC:746): (argininosuccinate lyase) This gene encodes a member of the lyase 1 family. The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. A nontranscribed pseudogene is also located on the long arm of chromosome 22. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 7-66081579-CA-C is Benign according to our data. Variant chr7-66081579-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1193577.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASL	NM_000048.4	c.13-209del		intron_variant		ENST00000304874.14
ASL	NM_001024943.2	c.13-209del		intron_variant
ASL	NM_001024944.2	c.13-209del		intron_variant
ASL	NM_001024946.2	c.13-209del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASL	ENST00000304874.14	c.13-209del		intron_variant		1	NM_000048.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 476 AN: 115074 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00553

Gnomad ASJ AF: 0.00175

Gnomad EAS AF: 0.00238

Gnomad SAS AF: 0.000276

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.00408

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00421 AC: 484 AN: 115098 Hom.: 0 Cov.: 31 AF XY: 0.00525 AC XY: 287 AN XY: 54696

Gnomad4 AFR AF: 0.00225

Gnomad4 AMR AF: 0.00553

Gnomad4 ASJ AF: 0.00175

Gnomad4 EAS AF: 0.00239

Gnomad4 SAS AF: 0.000277

Gnomad4 FIN AF: 0.0247

Gnomad4 NFE AF: 0.00313

Gnomad4 OTH AF: 0.00471

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs113517237; hg19: chr7-65546566;