9-130499504-GCATGAAC-GC

Variant names:

• chr9-130499504-GCATGAA-G
• rs1439911743
• NM_054012.4:c.1129_1134delATGAAC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_054012.4(ASS1):​c.1129_1134delATGAAC​(p.Met377_Asn378del) variant causes a conservative inframe deletion, splice region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASS1 NM_054012.4 conservative_inframe_deletion, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.20
• Publications: 0 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, Myriad Women’s Health, G2P
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_054012.4.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	NM_054012.4	MANE Select	c.1129_1134delATGAAC	p.Met377_Asn378del	conservative_inframe_deletion splice_region	Exon 14 of 15	NP_446464.1
	ASS1	NM_000050.4		c.1129_1134delATGAAC	p.Met377_Asn378del	conservative_inframe_deletion splice_region	Exon 15 of 16	NP_000041.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASS1	ENST00000352480.10	TSL:1 MANE Select	c.1129_1134delATGAAC	p.Met377_Asn378del	conservative_inframe_deletion splice_region	Exon 14 of 15	ENSP00000253004.6
	ASS1	ENST00000372393.7	TSL:5	c.1129_1134delATGAAC	p.Met377_Asn378del	conservative_inframe_deletion splice_region	Exon 15 of 16	ENSP00000361469.2
	ASS1	ENST00000372394.5	TSL:2	c.1129_1134delATGAAC	p.Met377_Asn378del	conservative_inframe_deletion splice_region	Exon 15 of 16	ENSP00000361471.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2
Mutation Taster		=49/151	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1439911743; hg19: chr9-133374891;