chr9-130470839-C-T

Position:

chr9-130470839-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_054012.4(ASS1):c.501C>T(p.His167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,678 control chromosomes in the GnomAD database, including 12,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1190 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11429 hom. )

Consequence

ASS1
NM_054012.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.94

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 9-130470839-C-T is Benign according to our data. Variant chr9-130470839-C-T is described in ClinVar as [Benign]. Clinvar id is 92369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-130470839-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASS1	NM_054012.4 linkuse as main transcript	c.501C>T	p.His167=	synonymous_variant	7/15	ENST00000352480.10	NP_446464.1
ASS1	NM_000050.4 linkuse as main transcript	c.501C>T	p.His167=	synonymous_variant	8/16		NP_000041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10 linkuse as main transcript	c.501C>T	p.His167=	synonymous_variant	7/15	1	NM_054012.4	ENSP00000253004	P1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18250

AN:

152100

Hom.:

1192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.0992

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0316

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.126

GnomAD3 exomes

AF:

0.114

AC:

28765

AN:

251434

Hom.:

1905

AF XY:

0.117

AC XY:

15934

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0680

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.0287

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.122

AC:

178862

AN:

1461460

Hom.:

11429

Cov.:

AF XY:

0.123

AC XY:

89214

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.0704

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.0274

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.120

AC:

18260

AN:

152218

Hom.:

1190

Cov.:

AF XY:

0.122

AC XY:

9087

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.0990

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.0311

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.117

Hom.:

1814

Bravo

AF:

0.112

Asia WGS

AF:

0.0770

AC:

269

AN:

3478

EpiCase

AF:

0.126

EpiControl

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 03, 2012	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Citrullinemia type I

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Mar 28, 2017	- -

Citrullinemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.32

DANN

Benign

0.52

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

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