rs553696

chr9-130486627-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054012.4(ASS1):c.839-2706A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,118 control chromosomes in the GnomAD database, including 8,896 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 0.33 (8896 hom., cov: 32)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4	c.839-2706A>G		intron_variant		ENST00000352480.10
ASS1	NM_000050.4	c.839-2706A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASS1	ENST00000352480.10	c.839-2706A>G		intron_variant		1	NM_054012.4	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50134 AN: 152000 Hom.: 8889 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.330 AC: 50179 AN: 152118 Hom.: 8896 Cov.: 32 AF XY: 0.335 AC XY: 24871 AN XY: 74350

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.337

Alfa AF: 0.334 Hom.: 4445

Bravo AF: 0.333

Asia WGS AF: 0.570 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.2
Dann	Benign	0.62

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: rs553696; hg19: chr9-133362014;