Variant 9-130489245-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_054012.4(ASS1):c.839-88A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 147,852 control chromosomes in the GnomAD database, including 31,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 31044 hom., cov: 27)

Exomes 𝑓: 0.54 ( 99820 hom. )

Failed GnomAD Quality Control

Consequence

ASS1
NM_054012.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.26

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 9-130489245-A-T is Benign according to our data. Variant chr9-130489245-A-T is described in ClinVar as [Benign]. Clinvar id is 1229182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASS1	NM_054012.4 link	c.839-88A>T		intron_variant		ENST00000352480.10	NP_446464.1	P00966Q5T6L4
ASS1	NM_000050.4 link	c.839-88A>T		intron_variant			NP_000041.2	P00966Q5T6L4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASS1	ENST00000352480.10 link	c.839-88A>T		intron_variant		1	NM_054012.4	ENSP00000253004.6		P00966

Frequencies

GnomAD3 genomes

AF:

0.623

AC:

92093

AN:

147778

Hom.:

31036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.759

Gnomad EAS

AF:

0.892

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.659

Gnomad NFE

AF:

0.727

Gnomad OTH

AF:

0.656

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.543

AC:

657419

AN:

1210158

Hom.:

99820

AF XY:

0.542

AC XY:

329200

AN XY:

607710

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.579

Gnomad4 ASJ exome

AF:

0.531

Gnomad4 EAS exome

AF:

0.586

Gnomad4 SAS exome

AF:

0.537

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.550

Gnomad4 OTH exome

AF:

0.532

GnomAD4 genome

AF:

0.623

AC:

92119

AN:

147852

Hom.:

31044

Cov.:

AF XY:

0.625

AC XY:

45028

AN XY:

72080

show subpopulations

Gnomad4 AFR

AF:

0.325

Gnomad4 AMR

AF:

0.752

Gnomad4 ASJ

AF:

0.759

Gnomad4 EAS

AF:

0.892

Gnomad4 SAS

AF:

0.781

Gnomad4 FIN

AF:

0.636

Gnomad4 NFE

AF:

0.727

Gnomad4 OTH

AF:

0.660

Alfa

AF:

0.340

Hom.:

622

Bravo

AF:

0.611

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.5

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over