9-130471533-A-G

Variant names:

• chr9-130471533-A-G
• rs652313
• NM_054012.4:c.597+18A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_054012.4(ASS1):​c.597+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,612,552 control chromosomes in the GnomAD database, including 597,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (48267 hom., cov: 32)
  • Exomes 𝑓: 0.87 (549611 hom.)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -2.94
• Publications: 16 publications found

Genes affected

ASS1 (HGNC:758): (argininosuccinate synthase 1) The protein encoded by this gene catalyzes the penultimate step of the arginine biosynthetic pathway. There are approximately 10 to 14 copies of this gene including the pseudogenes scattered across the human genome, among which the one located on chromosome 9 appears to be the only functional gene for argininosuccinate synthetase. Mutations in the chromosome 9 copy of this gene cause citrullinemia. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2012]

ASS1 Gene-Disease associations (from GenCC):

• citrullinemia type I

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, G2P
• acute neonatal citrullinemia type I

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• adult-onset citrullinemia type I

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-130471533-A-G is Benign according to our data. Variant chr9-130471533-A-G is described in ClinVar as Benign. ClinVar VariationId is 92370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	NM_054012.4	MANE Select	c.597+18A>G		intron	N/A	NP_446464.1
	ASS1	NM_000050.4		c.597+18A>G		intron	N/A	NP_000041.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	ENST00000352480.10	TSL:1 MANE Select	c.597+18A>G		intron	N/A	ENSP00000253004.6
	ASS1	ENST00000372393.7	TSL:5	c.597+18A>G		intron	N/A	ENSP00000361469.2
	ASS1	ENST00000372394.5	TSL:2	c.597+18A>G		intron	N/A	ENSP00000361471.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119105 AN: 151924 Hom.: 48250 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.789

GnomAD2 exomes AF: 0.856 AC: 215054 AN: 251298 AF XY: 0.859

Gnomad AFR exome AF: 0.550

Gnomad AMR exome AF: 0.903

Gnomad ASJ exome AF: 0.847

Gnomad EAS exome AF: 0.970

Gnomad FIN exome AF: 0.820

Gnomad NFE exome AF: 0.871

Gnomad OTH exome AF: 0.854

GnomAD4 exome AF: 0.865 AC: 1264067 AN: 1460510 Hom.: 549611 Cov.: 48 AF XY: 0.866 AC XY: 629090 AN XY: 726656

African (AFR) AF: 0.537 AC: 17959 AN: 33426

American (AMR) AF: 0.900 AC: 40241 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 22038 AN: 26126

East Asian (EAS) AF: 0.973 AC: 38618 AN: 39696

South Asian (SAS) AF: 0.867 AC: 74776 AN: 86200

European-Finnish (FIN) AF: 0.827 AC: 44160 AN: 53378

Middle Eastern (MID) AF: 0.812 AC: 4678 AN: 5762

European-Non Finnish (NFE) AF: 0.874 AC: 970414 AN: 1110852

Other (OTH) AF: 0.848 AC: 51183 AN: 60356

GnomAD4 genome AF: 0.784 AC: 119171 AN: 152042 Hom.: 48267 Cov.: 32 AF XY: 0.785 AC XY: 58339 AN XY: 74336

African (AFR) AF: 0.559 AC: 23147 AN: 41412

American (AMR) AF: 0.848 AC: 12965 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2973 AN: 3472

East Asian (EAS) AF: 0.968 AC: 4990 AN: 5154

South Asian (SAS) AF: 0.864 AC: 4166 AN: 4822

European-Finnish (FIN) AF: 0.823 AC: 8719 AN: 10588

Middle Eastern (MID) AF: 0.798 AC: 233 AN: 292

European-Non Finnish (NFE) AF: 0.875 AC: 59523 AN: 67992

Other (OTH) AF: 0.791 AC: 1670 AN: 2110

Alfa AF: 0.849 Hom.: 42211

Bravo AF: 0.774

Asia WGS AF: 0.899 AC: 3126 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Citrullinemia type I Benign:4

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 22, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 09, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not specified Benign:3

Apr 20, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Citrullinemia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.38
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs652313; hg19: chr9-133346920;