3-183840793-G-C

Position:

• chr3-183840793-G-C

Variant summary

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

The NM_018622.7(PARL):​c.758-153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 150,226 control chromosomes in the GnomAD database, including 7,319 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 0.29 (7306 hom., cov: 29)
  • Exomes 𝑓: 0.15 (13 hom.)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARL	NM_018622.7	c.758-153C>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.758-153C>G		intron_variant		1	NM_018622.7	ENSP00000325421	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43098 AN: 149318 Hom.: 7265 Cov.: 29

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.149 AC: 118 AN: 794 Hom.: 13 AF XY: 0.161 AC XY: 67 AN XY: 416

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.125

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.289 AC: 43206 AN: 149432 Hom.: 7306 Cov.: 29 AF XY: 0.291 AC XY: 21125 AN XY: 72656

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.287

Alfa AF: 0.113 Hom.: 185

Bravo AF: 0.298

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.36

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: rs12636826; hg19: chr3-183558581;