3-183844488-A-C

Position:

• chr3-183844488-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018622.7(PARL):​c.512-162T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 621,298 control chromosomes in the GnomAD database, including 65,056 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 (14020 hom., cov: 32)
  • Exomes 𝑓: 0.46 (51036 hom.)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARL	NM_018622.7	c.512-162T>G		intron_variant		ENST00000317096.9	NP_061092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9	c.512-162T>G		intron_variant		1	NM_018622.7	ENSP00000325421	P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64120 AN: 151948 Hom.: 14020 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.462 AC: 216643 AN: 469232 Hom.: 51036 Cov.: 4 AF XY: 0.461 AC XY: 116192 AN XY: 251952

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.511

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.422 AC: 64125 AN: 152066 Hom.: 14020 Cov.: 32 AF XY: 0.416 AC XY: 30903 AN XY: 74344

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.449

Alfa AF: 0.485 Hom.: 37035

Bravo AF: 0.434

Asia WGS AF: 0.406 AC: 1413 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3811725; hg19: chr3-183562276;