7-66081579-CA-C

Variant names:

• chr7-66081579-CA-C
• rs113517237
• NM_000048.4:c.13-209delA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000048.4(ASL):​c.13-209delA 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
• 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 -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 rank	MANE	Protein	UniProt
ASL	NM_000048.4	c.13-209delA		intron_variant	Intron 2 of 16	ENST00000304874.14	NP_000039.2
ASL	NM_001024943.2	c.13-209delA		intron_variant	Intron 1 of 15		NP_001020114.1
ASL	NM_001024944.2	c.13-209delA		intron_variant	Intron 1 of 14		NP_001020115.1
ASL	NM_001024946.2	c.13-209delA		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.13-223delA		intron_variant	Intron 2 of 16	1	NM_000048.4	ENSP00000307188.9

Frequencies

GnomAD3 genomes AF: 0.00414 AC: 476 AN: 115074 Hom.: 0 Cov.: 31

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00225 AC: 69 AN: 30638

American (AMR) AF: 0.00553 AC: 60 AN: 10852

Ashkenazi Jewish (ASJ) AF: 0.00175 AC: 5 AN: 2862

East Asian (EAS) AF: 0.00239 AC: 10 AN: 4184

South Asian (SAS) AF: 0.000277 AC: 1 AN: 3610

European-Finnish (FIN) AF: 0.0247 AC: 162 AN: 6566

Middle Eastern (MID) AF: 0.00450 AC: 1 AN: 222

European-Non Finnish (NFE) AF: 0.00313 AC: 169 AN: 53974

Other (OTH) AF: 0.00471 AC: 7 AN: 1486

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 20, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism

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

dbSNP: rs113517237; hg19: chr7-65546566;