9-130482639-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054012.4. 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
	ASS1	NM_054012.4	MANE Select	c.838+2190A>G		intron	N/A	NP_446464.1	Q5T6L4
	ASS1	NM_000050.4		c.838+2190A>G		intron	N/A	NP_000041.2	P00966

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	ENST00000352480.10	TSL:1 MANE Select	c.838+2190A>G		intron	N/A	ENSP00000253004.6	P00966
	ASS1	ENST00000852201.1		c.1033+2190A>G		intron	N/A	ENSP00000522260.1
	ASS1	ENST00000852207.1		c.838+2190A>G		intron	N/A	ENSP00000522266.1

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

African (AFR) AF: 0.158 AC: 6562 AN: 41446

American (AMR) AF: 0.0665 AC: 1016 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5178

South Asian (SAS) AF: 0.0701 AC: 337 AN: 4810

European-Finnish (FIN) AF: 0.178 AC: 1884 AN: 10578

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7346 AN: 67956

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.42
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12555797; hg19: chr9-133358026;