7-66076113-C-A

Variant names:

• chr7-66076113-C-A
• NM_000048.4:c.12+20C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000048.4(ASL):​c.12+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASL NM_000048.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

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]

ASL Gene-Disease associations (from GenCC):

• argininosuccinic aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 7-66076113-C-A is Benign according to our data. Variant chr7-66076113-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2853137.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASL	NM_000048.4	c.12+20C>A		intron_variant	Intron 2 of 16	ENST00000304874.14	NP_000039.2
ASL	NM_001024943.2	c.12+20C>A		intron_variant	Intron 1 of 15		NP_001020114.1
ASL	NM_001024944.2	c.12+20C>A		intron_variant	Intron 1 of 14		NP_001020115.1
ASL	NM_001024946.2	c.12+20C>A		intron_variant	Intron 1 of 14		NP_001020117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASL	ENST00000304874.14	c.12+20C>A		intron_variant	Intron 2 of 16	1	NM_000048.4	ENSP00000307188.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1436742 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 712466

African (AFR) AF: 0.00 AC: 0 AN: 32938

American (AMR) AF: 0.00 AC: 0 AN: 41440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25614

East Asian (EAS) AF: 0.00 AC: 0 AN: 38412

South Asian (SAS) AF: 0.00 AC: 0 AN: 82420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100398

Other (OTH) AF: 0.00 AC: 0 AN: 59438

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Argininosuccinate lyase deficiency Benign:1

Apr 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		2.5
PromoterAI		0.066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

hg19: chr7-65541100;