rs10793902

Variant names:

• chr9-130502523-C-T
• rs10793902
• ENST00000852176.1:c.*1502C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000852176.1(ASS1):​c.*1502C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,916 control chromosomes in the GnomAD database, including 21,037 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21037 hom., cov: 31)
• Consequence: ASS1 ENST00000852176.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 7 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, G2P, Myriad Women’s Health
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000852176.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	ENST00000852176.1		c.*1502C>T		downstream_gene	N/A	ENSP00000522235.1
	ASS1	ENST00000852178.1		c.*1502C>T		downstream_gene	N/A	ENSP00000522237.1
	ASS1	ENST00000852179.1		c.*1502C>T		downstream_gene	N/A	ENSP00000522238.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78869 AN: 151798 Hom.: 21035 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.519 AC: 78887 AN: 151916 Hom.: 21037 Cov.: 31 AF XY: 0.524 AC XY: 38897 AN XY: 74244

African (AFR) AF: 0.435 AC: 18020 AN: 41428

American (AMR) AF: 0.457 AC: 6965 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2340 AN: 3466

East Asian (EAS) AF: 0.361 AC: 1856 AN: 5136

South Asian (SAS) AF: 0.510 AC: 2458 AN: 4816

European-Finnish (FIN) AF: 0.645 AC: 6802 AN: 10544

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38634 AN: 67962

Other (OTH) AF: 0.551 AC: 1160 AN: 2106

Alfa AF: 0.553 Hom.: 53687

Bravo AF: 0.498

Asia WGS AF: 0.404 AC: 1408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.80
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs10793902; hg19: chr9-133377910; COSMIC: COSV61688830;