9-130471523-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_054012.4(ASS1):c.597+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00896 in 1,613,784 control chromosomes in the GnomAD database, including 977 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 516 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 461 hom. )

Consequence

ASS1
NM_054012.4 splice_region, intron

Scores

Splicing: ADA: 0.0001715

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0630

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-130471523-C-T is Benign according to our data. Variant chr9-130471523-C-T is described in ClinVar as [Benign]. Clinvar id is 254747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-130471523-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASS1	NM_054012.4 link	c.597+8C>T		splice_region_variant, intron_variant	Intron 8 of 14	ENST00000352480.10	NP_446464.1	P00966Q5T6L4
ASS1	NM_000050.4 link	c.597+8C>T		splice_region_variant, intron_variant	Intron 9 of 15		NP_000041.2	P00966Q5T6L4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10 link	c.597+8C>T		splice_region_variant, intron_variant	Intron 8 of 14	1	NM_054012.4	ENSP00000253004.6		P00966

Frequencies

GnomAD3 genomes

AF:

0.0454

AC:

6906

AN:

152142

Hom.:

513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0122

AC:

3078

AN:

251386

Hom.:

205

AF XY:

0.00912

AC XY:

1239

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.00963

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000871

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.00515

AC:

7533

AN:

1461524

Hom.:

461

Cov.:

AF XY:

0.00448

AC XY:

3255

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000680

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.0455

AC:

6926

AN:

152260

Hom.:

516

Cov.:

AF XY:

0.0437

AC XY:

3251

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0187

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0294

Hom.:

140

Bravo

AF:

0.0515

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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 type I

Benign:2

May 05, 2017

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.4

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over