3-183867753-T-C

Position:

• chr3-183867753-T-C

Variant summary

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

The NM_018622.7(PARL):​c.321+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 789,124 control chromosomes in the GnomAD database, including 192,972 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 0.70 (37767 hom., cov: 30)
  • Exomes 𝑓: 0.69 (155205 hom.)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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]

ENSG00000283765 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARL	NM_018622.7	c.321+112A>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.321+112A>G		intron_variant		1	NM_018622.7	ENSP00000325421.5
ENSG00000283765	ENST00000639401.1	c.321+112A>G		intron_variant		5		ENSP00000491227.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106541 AN: 151788 Hom.: 37715 Cov.: 30

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.728

GnomAD4 exome AF: 0.693 AC: 441442 AN: 637222 Hom.: 155205 AF XY: 0.692 AC XY: 238949 AN XY: 345510

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.764

Gnomad4 EAS exome AF: 0.899

Gnomad4 SAS exome AF: 0.698

Gnomad4 FIN exome AF: 0.590

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.699

GnomAD4 genome AF: 0.702 AC: 106647 AN: 151902 Hom.: 37767 Cov.: 30 AF XY: 0.698 AC XY: 51818 AN XY: 74246

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.733

Alfa AF: 0.683 Hom.: 48030

Bravo AF: 0.722

Asia WGS AF: 0.820 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.7
DANN	Benign	0.59

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: rs1402000; hg19: chr3-183585541; COSMIC: COSV57702989;