chr9-130452052-T-C

Position:

• chr9-130452052-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_054012.4(ASS1):​c.-5-172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 700,902 control chromosomes in the GnomAD database, including 330,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68584 hom., cov: 32)
  • Exomes 𝑓: 0.98 (262034 hom.)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.15

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 9-130452052-T-C is Benign according to our data. Variant chr9-130452052-T-C is described in ClinVar as [Benign]. Clinvar id is 683297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASS1	NM_054012.4	c.-5-172T>C		intron_variant		ENST00000352480.10	NP_446464.1
ASS1	NM_000050.4	c.-5-172T>C		intron_variant			NP_000041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10	c.-5-172T>C		intron_variant		1	NM_054012.4	ENSP00000253004	P1
ASS1	ENST00000372393.7	c.-5-172T>C		intron_variant		5		ENSP00000361469	P1
ASS1	ENST00000372394.5	c.-6+9T>C		intron_variant		2		ENSP00000361471	P1
ASS1	ENST00000422569.5	c.-5-172T>C		intron_variant		5		ENSP00000394212

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144125 AN: 152122 Hom.: 68533 Cov.: 32

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.955

GnomAD3 exomes AF: 0.974 AC: 136120 AN: 139790 Hom.: 66339 AF XY: 0.974 AC XY: 73312 AN XY: 75276

Gnomad AFR exome AF: 0.855

Gnomad AMR exome AF: 0.986

Gnomad ASJ exome AF: 0.959

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.964

Gnomad FIN exome AF: 0.968

Gnomad NFE exome AF: 0.985

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.977 AC: 536039 AN: 548662 Hom.: 262034 Cov.: 5 AF XY: 0.977 AC XY: 290060 AN XY: 296822

Gnomad4 AFR exome AF: 0.857

Gnomad4 AMR exome AF: 0.985

Gnomad4 ASJ exome AF: 0.958

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.965

Gnomad4 FIN exome AF: 0.969

Gnomad4 NFE exome AF: 0.985

Gnomad4 OTH exome AF: 0.972

GnomAD4 genome AF: 0.947 AC: 144233 AN: 152240 Hom.: 68584 Cov.: 32 AF XY: 0.947 AC XY: 70512 AN XY: 74438

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.975

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.956

Alfa AF: 0.955 Hom.: 8580

Bravo AF: 0.944

Asia WGS AF: 0.979 AC: 3405 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Citrullinemia type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.1
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs1760275; hg19: chr9-133327439;