9-130480593-C-T

Position:

• chr9-130480593-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_054012.4(ASS1):​c.838+144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 831,026 control chromosomes in the GnomAD database, including 93,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14821 hom., cov: 34)
  • Exomes 𝑓: 0.47 (79093 hom.)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.277

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-130480593-C-T is Benign according to our data. Variant chr9-130480593-C-T is described in ClinVar as [Benign]. Clinvar id is 1180898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4	c.838+144C>T		intron_variant		ENST00000352480.10
ASS1	NM_000050.4	c.838+144C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASS1	ENST00000352480.10	c.838+144C>T		intron_variant		1	NM_054012.4	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65126 AN: 152116 Hom.: 14812 Cov.: 34

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.471 AC: 319827 AN: 678792 Hom.: 79093 AF XY: 0.473 AC XY: 168218 AN XY: 355846

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.511

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.465

GnomAD4 genome AF: 0.428 AC: 65169 AN: 152234 Hom.: 14821 Cov.: 34 AF XY: 0.431 AC XY: 32096 AN XY: 74428

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.447

Alfa AF: 0.437 Hom.: 2999

Bravo AF: 0.427

Asia WGS AF: 0.625 AC: 2172 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.93
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2043190; hg19: chr9-133355980; COSMIC: COSV61688823; COSMIC: COSV61688823;