rs113517237

Variant names:

• chr7-66081579-CAAAA-C
• rs113517237
• NM_000048.4:c.13-212_13-209delAAAA

Your query was ambiguous. Multiple possible variants found:

• chr7-66081579-CAAAA-C
• chr7-66081579-CAAAA-CA
• chr7-66081579-CAAAA-CAA
• chr7-66081579-CAAAA-CAAA
• chr7-66081579-CAAAA-CAAAAA
• chr7-66081579-CAAAA-CAAAAAA
• chr7-66081579-CAAAA-CAAAAAAAA
• chr7-66081579-CAAAA-CAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000048.4(ASL):​c.13-212_13-209delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 115,344 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000026 (0 hom., cov: 31)
• Consequence: ASL NM_000048.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.600
• 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, Myriad Women’s Health

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000048.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASL	NM_000048.4	MANE Select	c.13-212_13-209delAAAA		intron	N/A	NP_000039.2
	ASL	NM_001024943.2		c.13-212_13-209delAAAA		intron	N/A	NP_001020114.1	A0A024RDL8
	ASL	NM_001024944.2		c.13-212_13-209delAAAA		intron	N/A	NP_001020115.1	P04424-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASL	ENST00000304874.14	TSL:1 MANE Select	c.13-223_13-220delAAAA		intron	N/A	ENSP00000307188.9	P04424-1
	ASL	ENST00000395332.8	TSL:1	c.13-223_13-220delAAAA		intron	N/A	ENSP00000378741.3	P04424-1
	ASL	ENST00000496336.1	TSL:1	n.254-223_254-220delAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000260 AC: 3 AN: 115344 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000150

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000185

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000260 AC: 3 AN: 115344 Hom.: 0 Cov.: 31 AF XY: 0.0000365 AC XY: 2 AN XY: 54812

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

African (AFR) AF: 0.0000327 AC: 1 AN: 30618

American (AMR) AF: 0.00 AC: 0 AN: 10882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2864

East Asian (EAS) AF: 0.00 AC: 0 AN: 4200

South Asian (SAS) AF: 0.00 AC: 0 AN: 3618

European-Finnish (FIN) AF: 0.000150 AC: 1 AN: 6662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000185 AC: 1 AN: 54084

Other (OTH) AF: 0.00 AC: 0 AN: 1476

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0225104), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.60

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;