3-183857982-G-A

Position:

• chr3-183857982-G-A

Variant summary

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

The NM_018622.7(PARL):​c.511+4771C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,216 control chromosomes in the GnomAD database, including 1,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (no stars).

• Frequency: Genomes: 𝑓 0.12 (1417 hom., cov: 32)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Uncertain risk allele no assertion criteria provided O:1
• Conservation: PhyloP100: 0.412

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARL	NM_018622.7	c.511+4771C>T		intron_variant		ENST00000317096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARL	ENST00000317096.9	c.511+4771C>T		intron_variant		1	NM_018622.7	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18314 AN: 152098 Hom.: 1402 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.123

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 18353 AN: 152216 Hom.: 1417 Cov.: 32 AF XY: 0.126 AC XY: 9345 AN XY: 74420

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.134

Alfa AF: 0.124 Hom.: 1278

Bravo AF: 0.116

Asia WGS AF: 0.246 AC: 852 AN: 3478

ClinVar

Significance: Uncertain risk allele

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Leprosy, susceptibility to, 1 Other:1

Uncertain risk allele, no assertion criteria provided

case-control

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Jun 10, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.74

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: rs12631031; hg19: chr3-183575770;