9-130483269-G-T

Position:

• chr9-130483269-G-T

Variant summary

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

The NM_054012.4(ASS1):​c.838+2820G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 151,058 control chromosomes in the GnomAD database, including 1,639 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 0.14 (1639 hom., cov: 29)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASS1	NM_054012.4	c.838+2820G>T		intron_variant		ENST00000352480.10	NP_446464.1
ASS1	NM_000050.4	c.838+2820G>T		intron_variant			NP_000041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10	c.838+2820G>T		intron_variant		1	NM_054012.4	ENSP00000253004	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21306 AN: 150940 Hom.: 1638 Cov.: 29

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.173

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.141 AC: 21321 AN: 151058 Hom.: 1639 Cov.: 29 AF XY: 0.142 AC XY: 10440 AN XY: 73734

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0286

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0653 Hom.: 90

Bravo AF: 0.136

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0040
DANN	Benign	0.85

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: rs10901080; hg19: chr9-133358656;