NM_001080379.2:c.700_702delCGCinsTTA

Variant names:

• chr6-163314913-CGC-TTA
• NM_001080379.2:c.700_702delCGCinsTTA
• PACRG p.Arg234Leu

Variant summary

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

The NM_001080379.2(PACRG):​c.700_702delCGCinsTTA​(p.Arg234Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R234H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PACRG NM_001080379.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58
• Publications: 0 publications found

Genes affected

PACRG (HGNC:19152): (parkin coregulated) This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson's disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson's disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PACRG-AS1 (HGNC:27772): (PACRG antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080379.2. 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
	PACRG	NM_001080379.2	MANE Select	c.700_702delCGCinsTTA	p.Arg234Leu	missense	N/A	NP_001073848.1	Q96M98-2
	PACRG	NM_152410.3		c.817_819delCGCinsTTA	p.Arg273Leu	missense	N/A	NP_689623.2	Q96M98-1
	PACRG	NM_001080378.2		c.700_702delCGCinsTTA	p.Arg234Leu	missense	N/A	NP_001073847.1	Q96M98-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACRG	ENST00000366888.7	TSL:1 MANE Select	c.700_702delCGCinsTTA	p.Arg234Leu	missense	N/A	ENSP00000355854.2	Q96M98-2
	PACRG	ENST00000366889.6	TSL:1	c.700_702delCGCinsTTA	p.Arg234Leu	missense	N/A	ENSP00000355855.2	Q96M98-2
	PACRG	ENST00000337019.7	TSL:2	c.817_819delCGCinsTTA	p.Arg273Leu	missense	N/A	ENSP00000337946.3	Q96M98-1

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6

Splicing

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

hg19: chr6-163735945;