7-66081579-CAAAA-CAAAAAA

Variant names:

• chr7-66081579-C-CAA
• rs113517237
• NM_000048.4:c.13-210_13-209dupAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000048.4(ASL):​c.13-210_13-209dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000433 in 115,354 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 0.000043 (0 hom., cov: 31)
• Consequence: ASL NM_000048.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASL	NM_000048.4	c.13-210_13-209dupAA		intron_variant	Intron 2 of 16	ENST00000304874.14	NP_000039.2
ASL	NM_001024943.2	c.13-210_13-209dupAA		intron_variant	Intron 1 of 15		NP_001020114.1
ASL	NM_001024944.2	c.13-210_13-209dupAA		intron_variant	Intron 1 of 14		NP_001020115.1
ASL	NM_001024946.2	c.13-210_13-209dupAA		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.13-224_13-223insAA		intron_variant	Intron 2 of 16	1	NM_000048.4	ENSP00000307188.9

Frequencies

GnomAD3 genomes AF: 0.0000433 AC: 5 AN: 115354 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000238

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000300

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000370

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000433 AC: 5 AN: 115354 Hom.: 0 Cov.: 31 AF XY: 0.0000365 AC XY: 2 AN XY: 54820

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000238

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000300

Gnomad4 NFE AF: 0.0000370

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;