3-183885155-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000445165.2(ENSG00000293259):​n.232C>T 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 0.447 in 531,368 control chromosomes in the GnomAD database, including 54,328 homozygotes. 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: 𝑓 0.42 (13830 hom., cov: 32)
  • Exomes 𝑓: 0.46 (40498 hom.)
• Consequence: ENSG00000293259 ENST00000445165.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

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>T		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000293259	ENST00000833400.1		n.119C>T		non_coding_transcript_exon	Exon 1 of 2
	PARL	ENST00000639100.1	TSL:5	c.-841G>A		upstream_gene	N/A	ENSP00000491186.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63699 AN: 151948 Hom.: 13828 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.458 AC: 173671 AN: 379302 Hom.: 40498 Cov.: 3 AF XY: 0.457 AC XY: 91004 AN XY: 199040

African (AFR) AF: 0.333 AC: 3656 AN: 10974

American (AMR) AF: 0.506 AC: 8298 AN: 16390

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 6370 AN: 11744

East Asian (EAS) AF: 0.456 AC: 11380 AN: 24972

South Asian (SAS) AF: 0.420 AC: 18877 AN: 44938

European-Finnish (FIN) AF: 0.328 AC: 7544 AN: 23024

Middle Eastern (MID) AF: 0.555 AC: 902 AN: 1624

European-Non Finnish (NFE) AF: 0.477 AC: 106661 AN: 223746

Other (OTH) AF: 0.456 AC: 9983 AN: 21890

GnomAD4 genome AF: 0.419 AC: 63723 AN: 152066 Hom.: 13830 Cov.: 32 AF XY: 0.412 AC XY: 30642 AN XY: 74352

African (AFR) AF: 0.326 AC: 13517 AN: 41472

American (AMR) AF: 0.480 AC: 7337 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2181 AN: 5162

South Asian (SAS) AF: 0.418 AC: 2017 AN: 4822

European-Finnish (FIN) AF: 0.289 AC: 3061 AN: 10580

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32306 AN: 67964

Other (OTH) AF: 0.448 AC: 948 AN: 2114

Alfa AF: 0.446 Hom.: 2546

Bravo AF: 0.435

Asia WGS AF: 0.416 AC: 1449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.0
DANN	Benign	0.74
PhyloP100		-0.54
PromoterAI		0.025	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; COSMIC: COSV57700275;