rs3792587

Variant names:

• chr3-183885155-C-A
• rs3792587
• ENST00000445165.2:n.232C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-183885155-C-A
• chr3-183885155-C-T

Variant summary

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

The ENST00000445165.2(ENSG00000293259):​n.232C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000263 in 379,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: ENSG00000293259 ENST00000445165.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 0 publications found

Genes affected

ENSG00000293259 (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=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445165.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293259	ENST00000445165.2	TSL:2	n.232C>A		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000293259	ENST00000833400.1		n.119C>A		non_coding_transcript_exon	Exon 1 of 2
	PARL	ENST00000639100.1	TSL:5	c.-841G>T		upstream_gene	N/A	ENSP00000491186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000263 AC: 1 AN: 379906 Hom.: 0 Cov.: 3 AF XY: 0.00000502 AC XY: 1 AN XY: 199344

African (AFR) AF: 0.00 AC: 0 AN: 10990

American (AMR) AF: 0.00 AC: 0 AN: 16400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11772

East Asian (EAS) AF: 0.00 AC: 0 AN: 25032

South Asian (SAS) AF: 0.0000222 AC: 1 AN: 44962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 224134

Other (OTH) AF: 0.00 AC: 0 AN: 21922

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.52
PhyloP100		-0.54
PromoterAI		0.020	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3792587; hg19: chr3-183602943;