rs553696

Variant names:

• chr9-130486627-A-G
• rs553696
• NM_054012.4:c.839-2706A>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.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
• Publications: 6 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, Myriad Women’s Health, G2P
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	NM_054012.4	MANE Select	c.839-2706A>G		intron	N/A	NP_446464.1
	ASS1	NM_000050.4		c.839-2706A>G		intron	N/A	NP_000041.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	ENST00000352480.10	TSL:1 MANE Select	c.839-2706A>G		intron	N/A	ENSP00000253004.6
	ASS1	ENST00000372393.7	TSL:5	c.839-2706A>G		intron	N/A	ENSP00000361469.2
	ASS1	ENST00000372394.5	TSL:2	c.839-2706A>G		intron	N/A	ENSP00000361471.1

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

African (AFR) AF: 0.254 AC: 10525 AN: 41504

American (AMR) AF: 0.423 AC: 6468 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1052 AN: 3468

East Asian (EAS) AF: 0.610 AC: 3153 AN: 5170

South Asian (SAS) AF: 0.478 AC: 2305 AN: 4824

European-Finnish (FIN) AF: 0.308 AC: 3261 AN: 10584

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22239 AN: 67984

Other (OTH) AF: 0.337 AC: 709 AN: 2104

Alfa AF: 0.333 Hom.: 4868

Bravo AF: 0.333

Asia WGS AF: 0.570 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		0.27
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: rs553696; hg19: chr9-133362014;