9-130482639-A-G

Variant names:

• chr9-130482639-A-G
• rs12555797
• NM_054012.4:c.838+2190A>G

Variant summary

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

The NM_054012.4(ASS1):​c.838+2190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,042 control chromosomes in the GnomAD database, including 1,176 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 0.12 (1176 hom., cov: 30)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASS1	NM_054012.4	c.838+2190A>G		intron_variant	Intron 11 of 14	ENST00000352480.10	NP_446464.1
ASS1	NM_000050.4	c.838+2190A>G		intron_variant	Intron 12 of 15		NP_000041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10	c.838+2190A>G		intron_variant	Intron 11 of 14	1	NM_054012.4	ENSP00000253004.6

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17705 AN: 151924 Hom.: 1175 Cov.: 30

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0871

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

GnomAD4 genome AF: 0.117 AC: 17731 AN: 152042 Hom.: 1176 Cov.: 30 AF XY: 0.118 AC XY: 8751 AN XY: 74324

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0701

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0695 Hom.: 77

Bravo AF: 0.111

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.42

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: rs12555797; hg19: chr9-133358026;