9-130483269-G-T

Variant names:

• chr9-130483269-G-T
• rs10901080
• NM_054012.4:c.838+2820G>T

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+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
• Publications: 8 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.838+2820G>T		intron	N/A	NP_446464.1
	ASS1	NM_000050.4		c.838+2820G>T		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.838+2820G>T		intron	N/A	ENSP00000253004.6
	ASS1	ENST00000372393.7	TSL:5	c.838+2820G>T		intron	N/A	ENSP00000361469.2
	ASS1	ENST00000372394.5	TSL:2	c.838+2820G>T		intron	N/A	ENSP00000361471.1

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

African (AFR) AF: 0.172 AC: 7062 AN: 41108

American (AMR) AF: 0.108 AC: 1643 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3466

East Asian (EAS) AF: 0.0286 AC: 146 AN: 5104

South Asian (SAS) AF: 0.132 AC: 620 AN: 4710

European-Finnish (FIN) AF: 0.177 AC: 1839 AN: 10390

Middle Eastern (MID) AF: 0.169 AC: 49 AN: 290

European-Non Finnish (NFE) AF: 0.134 AC: 9113 AN: 67814

Other (OTH) AF: 0.144 AC: 302 AN: 2094

Alfa AF: 0.123 Hom.: 1534

Bravo AF: 0.136

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0040
DANN	Benign	0.85
PhyloP100		-3.2
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: rs10901080; hg19: chr9-133358656;