9-130450085-T-C

Variant summary

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

The NM_054012.4(ASS1):c.-5-2139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,178 control chromosomes in the GnomAD database, including 46,055 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 0.78 (46055 hom., cov: 33)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4	c.-5-2139T>C		intron_variant		ENST00000352480.10
ASS1	NM_000050.4	c.-67-187T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASS1	ENST00000352480.10	c.-5-2139T>C		intron_variant		1	NM_054012.4	P1
ASS1	ENST00000372393.7	c.-67-187T>C		intron_variant		5		P1
ASS1	ENST00000372394.5	c.-447-1517T>C		intron_variant		2		P1
ASS1	ENST00000422569.5	c.-5-2139T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118041 AN: 152060 Hom.: 46010 Cov.: 33

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.776 AC: 118148 AN: 152178 Hom.: 46055 Cov.: 33 AF XY: 0.777 AC XY: 57816 AN XY: 74392

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.774

Alfa AF: 0.756 Hom.: 54672

Bravo AF: 0.775

Asia WGS AF: 0.792 AC: 2755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.31
Dann	Benign	0.48

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: rs4740158; hg19: chr9-133325472;