rs868834862

Variant names:

• chr7-66089173-C-A
• NM_000048.4:c.916C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-66089173-C-A
• chr7-66089173-C-G
• chr7-66089173-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4 BP6_Moderate BP7

The NM_000048.4(ASL):​c.916C>A​(p.Arg306Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,344,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ASL NM_000048.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.8932
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.78

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]

ENSG00000249319 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).
• BP6: Variant 7-66089173-C-A is Benign according to our data. Variant chr7-66089173-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2795751.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASL	NM_000048.4	c.916C>A	p.Arg306Arg	splice_region_variant, synonymous_variant	Exon 12 of 17	ENST00000304874.14	NP_000039.2
ASL	NM_001024943.2	c.916C>A	p.Arg306Arg	splice_region_variant, synonymous_variant	Exon 11 of 16		NP_001020114.1
ASL	NM_001024944.2	c.916C>A	p.Arg306Arg	splice_region_variant, synonymous_variant	Exon 11 of 15		NP_001020115.1
ASL	NM_001024946.2	c.838C>A	p.Arg280Arg	splice_region_variant, synonymous_variant	Exon 10 of 15		NP_001020117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASL	ENST00000304874.14	c.916C>A	p.Arg306Arg	splice_region_variant, synonymous_variant	Exon 12 of 17	1	NM_000048.4	ENSP00000307188.9
ENSG00000249319	ENST00000450043.2	c.229C>A	p.Arg77Arg	splice_region_variant, synonymous_variant	Exon 3 of 12	5		ENSP00000396527.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1344438 Hom.: 0 Cov.: 34 AF XY: 0.00000149 AC XY: 1 AN XY: 672664

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.84e-7

Gnomad4 OTH exome AF: 0.00

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

Oct 11, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-65554160;