12-8059829-A-ATC

Variant names:

• chr12-8059829-A-ATC
• rs869312973
• NM_004054.4:c.355_356dupGA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_004054.4(C3AR1):​c.355_356dupGA​(p.Asp119GlufsTer19) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C3AR1 NM_004054.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.95
• Publications: 3 publications found

Genes affected

C3AR1 (HGNC:1319): (complement C3a receptor 1) C3a is an anaphylatoxin released during activation of the complement system. The protein encoded by this gene is an orphan G protein-coupled receptor for C3a. Binding of C3a by the encoded receptor activates chemotaxis, granule enzyme release, superoxide anion production, and bacterial opsonization. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-8059829-A-ATC is Pathogenic according to our data. Variant chr12-8059829-A-ATC is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 222958.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004054.4. 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
	C3AR1	NM_004054.4	MANE Select	c.355_356dupGA	p.Asp119GlufsTer19	frameshift	Exon 2 of 2	NP_004045.1
	C3AR1	NM_001326475.2		c.355_356dupGA	p.Asp119GlufsTer19	frameshift	Exon 2 of 2	NP_001313404.1
	C3AR1	NM_001326477.2		c.355_356dupGA	p.Asp119GlufsTer19	frameshift	Exon 2 of 2	NP_001313406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3AR1	ENST00000307637.5	TSL:1 MANE Select	c.355_356dupGA	p.Asp119GlufsTer19	frameshift	Exon 2 of 2	ENSP00000302079.4
	C3AR1	ENST00000904894.1		c.355_356dupGA	p.Asp119GlufsTer19	frameshift	Exon 2 of 2	ENSP00000574953.1
	C3AR1	ENST00000904895.1		c.355_356dupGA	p.Asp119GlufsTer19	frameshift	Exon 2 of 2	ENSP00000574954.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Hemolytic uremic syndrome, atypical, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9

Splicing

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

Other links and lift over

dbSNP: rs869312973; hg19: chr12-8212425;