9-130452131-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_054012.4(ASS1):c.-5-93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,123,830 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (5 hom.)
• Consequence: ASS1 NM_054012.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0590

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=-0.62).
• BP6: Variant 9-130452131-C-T is Benign according to our data. Variant chr9-130452131-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1214955.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00495 (754/152262) while in subpopulation AFR AF= 0.0175 (728/41554). AF 95% confidence interval is 0.0165. There are 8 homozygotes in gnomad4. There are 374 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASS1	NM_054012.4	c.-5-93C>T		intron_variant		ENST00000352480.10
ASS1	NM_000050.4	c.-5-93C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASS1	ENST00000352480.10	c.-5-93C>T		intron_variant		1	NM_054012.4	P1
ASS1	ENST00000372393.7	c.-5-93C>T		intron_variant		5		P1
ASS1	ENST00000372394.5	c.-6+88C>T		intron_variant		2		P1
ASS1	ENST00000422569.5	c.-5-93C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00496 AC: 754 AN: 152142 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000474 AC: 461 AN: 971568 Hom.: 5 Cov.: 13 AF XY: 0.000426 AC XY: 212 AN XY: 497968

Gnomad4 AFR exome AF: 0.0159

Gnomad4 AMR exome AF: 0.000702

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000582

Gnomad4 OTH exome AF: 0.00125

GnomAD4 genome AF: 0.00495 AC: 754 AN: 152262 Hom.: 8 Cov.: 32 AF XY: 0.00502 AC XY: 374 AN XY: 74462

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00416 Hom.: 0

Bravo AF: 0.00559

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	5.4
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs75950322; hg19: chr9-133327518;