rs263003

Variant names:

• chr3-183829177-C-G
• rs263003
• ENST00000639401.1:c.1028+4315G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-183829177-C-G
• chr3-183829177-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000639401.1(ENSG00000283765):​c.1028+4315G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000283765 ENST00000639401.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• Publications: 7 publications found

Genes affected

ENSG00000283765 (HGNC:):

PARL (HGNC:18253): (presenilin associated rhomboid like) This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000639401.1. 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
	PARL	NM_018622.7	MANE Select	c.*421G>C		downstream_gene	N/A	NP_061092.3
	PARL	NM_001324436.2		c.*421G>C		downstream_gene	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.*421G>C		downstream_gene	N/A	NP_001032728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283765	ENST00000639401.1	TSL:5	c.1028+4315G>C		intron	N/A	ENSP00000491227.1
	PARL	ENST00000317096.9	TSL:1 MANE Select	c.*421G>C		downstream_gene	N/A	ENSP00000325421.5
	PARL	ENST00000311101.9	TSL:1	c.*421G>C		downstream_gene	N/A	ENSP00000310676.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 88506 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 46112

African (AFR) AF: 0.00 AC: 0 AN: 3658

American (AMR) AF: 0.00 AC: 0 AN: 4798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2154

East Asian (EAS) AF: 0.00 AC: 0 AN: 5536

South Asian (SAS) AF: 0.00 AC: 0 AN: 10460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53686

Other (OTH) AF: 0.00 AC: 0 AN: 4700

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.63
DANN	Benign	0.63
PhyloP100		-0.52

Splicing

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

Other links and lift over

dbSNP: rs263003; hg19: chr3-183546965;