rs13091

chr3-183842407-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018622.7(PARL):c.648T>C(p.His216=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,611,362 control chromosomes in the GnomAD database, including 183,246 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 0.47 (17230 hom., cov: 32)
  • Exomes 𝑓: 0.47 (166016 hom.)
• Consequence: PARL NM_018622.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARL	NM_018622.7	c.648T>C	p.His216=	synonymous_variant	6/10	ENST00000317096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARL	ENST00000317096.9	c.648T>C	p.His216=	synonymous_variant	6/10	1	NM_018622.7	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71948 AN: 151984 Hom.: 17223 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.505

GnomAD3 exomes AF: 0.468 AC: 117604 AN: 251232 Hom.: 28051 AF XY: 0.464 AC XY: 63063 AN XY: 135802

Gnomad AFR exome AF: 0.490

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.545

Gnomad EAS exome AF: 0.422

Gnomad SAS exome AF: 0.422

Gnomad FIN exome AF: 0.336

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.475 AC: 692821 AN: 1459260 Hom.: 166016 Cov.: 33 AF XY: 0.474 AC XY: 343841 AN XY: 726058

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.545

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.473 AC: 71971 AN: 152102 Hom.: 17230 Cov.: 32 AF XY: 0.466 AC XY: 34681 AN XY: 74350

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.499

Alfa AF: 0.489 Hom.: 7849

Bravo AF: 0.491

Asia WGS AF: 0.417 AC: 1454 AN: 3478

EpiCase AF: 0.498

EpiControl AF: 0.500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	6.9
Dann	Benign	0.55

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: rs13091; hg19: chr3-183560195; COSMIC: COSV57699961; COSMIC: COSV57699961;