rs10901072

Variant names:

• chr9-130470839-C-T
• rs10901072
• NM_054012.4:c.501C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_054012.4(ASS1):​c.501C>T​(p.His167His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,678 control chromosomes in the GnomAD database, including 12,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1190 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11429 hom.)
• Consequence: ASS1 NM_054012.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -2.94
• Publications: 16 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Myriad Women’s Health
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 9-130470839-C-T is Benign according to our data. Variant chr9-130470839-C-T is described in ClinVar as Benign. ClinVar VariationId is 92369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 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.501C>T	p.His167His	synonymous	Exon 7 of 15	NP_446464.1	Q5T6L4
	ASS1	NM_000050.4		c.501C>T	p.His167His	synonymous	Exon 8 of 16	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.501C>T	p.His167His	synonymous	Exon 7 of 15	ENSP00000253004.6	P00966
	ASS1	ENST00000852201.1		c.501C>T	p.His167His	synonymous	Exon 7 of 16	ENSP00000522260.1
	ASS1	ENST00000852207.1		c.501C>T	p.His167His	synonymous	Exon 7 of 16	ENSP00000522266.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18250 AN: 152100 Hom.: 1192 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0992

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.114 AC: 28765 AN: 251434 AF XY: 0.117

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.0680

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.0287

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.122 AC: 178862 AN: 1461460 Hom.: 11429 Cov.: 33 AF XY: 0.123 AC XY: 89214 AN XY: 727028

African (AFR) AF: 0.123 AC: 4108 AN: 33474

American (AMR) AF: 0.0704 AC: 3149 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3122 AN: 26132

East Asian (EAS) AF: 0.0274 AC: 1089 AN: 39700

South Asian (SAS) AF: 0.121 AC: 10403 AN: 86254

European-Finnish (FIN) AF: 0.192 AC: 10261 AN: 53330

Middle Eastern (MID) AF: 0.121 AC: 697 AN: 5768

European-Non Finnish (NFE) AF: 0.125 AC: 138791 AN: 1111708

Other (OTH) AF: 0.120 AC: 7242 AN: 60372

GnomAD4 genome AF: 0.120 AC: 18260 AN: 152218 Hom.: 1190 Cov.: 33 AF XY: 0.122 AC XY: 9087 AN XY: 74418

African (AFR) AF: 0.117 AC: 4845 AN: 41518

American (AMR) AF: 0.0990 AC: 1514 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3472

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5184

South Asian (SAS) AF: 0.125 AC: 604 AN: 4824

European-Finnish (FIN) AF: 0.193 AC: 2049 AN: 10604

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8316 AN: 68002

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.117 Hom.: 2165

Bravo AF: 0.112

Asia WGS AF: 0.0770 AC: 269 AN: 3478

EpiCase AF: 0.126

EpiControl AF: 0.131

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Citrullinemia type I (3)
-	-	1	Citrullinemia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.32
DANN	Benign	0.52
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10901072; hg19: chr9-133346226; COSMIC: COSV61688893;