rs543048

Variant names:

• chr9-130489245-A-T
• rs543048
• NM_054012.4:c.839-88A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-130489245-A-T
• chr9-130489245-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.26
• Publications: 4 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: Myriad Women's Health, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	NM_054012.4	MANE Select	c.839-88A>T		intron	N/A	NP_446464.1	Q5T6L4
	ASS1	NM_000050.4		c.839-88A>T		intron	N/A	NP_000041.2	P00966

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	ENST00000352480.10	TSL:1 MANE Select	c.839-88A>T		intron	N/A	ENSP00000253004.6	P00966
	ASS1	ENST00000852201.1		c.1034-88A>T		intron	N/A	ENSP00000522260.1
	ASS1	ENST00000852207.1		c.962-88A>T		intron	N/A	ENSP00000522266.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 92093 AN: 147778 Hom.: 31036 Cov.: 27

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

African (AFR) AF: 0.277 AC: 7162 AN: 25852

American (AMR) AF: 0.579 AC: 21447 AN: 37014

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 12065 AN: 22740

East Asian (EAS) AF: 0.586 AC: 20594 AN: 35166

South Asian (SAS) AF: 0.537 AC: 40329 AN: 75094

European-Finnish (FIN) AF: 0.515 AC: 20503 AN: 39824

Middle Eastern (MID) AF: 0.508 AC: 1782 AN: 3510

European-Non Finnish (NFE) AF: 0.550 AC: 506621 AN: 920342

Other (OTH) AF: 0.532 AC: 26916 AN: 50616

GnomAD4 genome AF: 0.623 AC: 92119 AN: 147852 Hom.: 31044 Cov.: 27 AF XY: 0.625 AC XY: 45028 AN XY: 72080

African (AFR) AF: 0.325 AC: 12825 AN: 39514

American (AMR) AF: 0.752 AC: 11260 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2619 AN: 3450

East Asian (EAS) AF: 0.892 AC: 4510 AN: 5056

South Asian (SAS) AF: 0.781 AC: 3680 AN: 4712

European-Finnish (FIN) AF: 0.636 AC: 6228 AN: 9800

Middle Eastern (MID) AF: 0.655 AC: 186 AN: 284

European-Non Finnish (NFE) AF: 0.727 AC: 48775 AN: 67102

Other (OTH) AF: 0.660 AC: 1359 AN: 2060

Alfa AF: 0.340 Hom.: 622

Bravo AF: 0.611

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-1.3
Mutation Taster		=74/26	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs543048;

hg19: chr9-133364632;