3-183884399-T-G

Position:

• chr3-183884399-T-G

Variant summary

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

The NM_018622.7(PARL):​c.125+323A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,128 control chromosomes in the GnomAD database, including 44,227 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 0.76 (44227 hom., cov: 33)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARL	NM_018622.7	c.125+323A>C		intron_variant		ENST00000317096.9	NP_061092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9	c.125+323A>C		intron_variant		1	NM_018622.7	ENSP00000325421.5
ENSG00000283765	ENST00000639401.1	c.125+323A>C		intron_variant		5		ENSP00000491227.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115481 AN: 152010 Hom.: 44173 Cov.: 33

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.760 AC: 115591 AN: 152128 Hom.: 44227 Cov.: 33 AF XY: 0.755 AC XY: 56130 AN XY: 74336

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.790

Alfa AF: 0.735 Hom.: 10075

Bravo AF: 0.777

Asia WGS AF: 0.856 AC: 2980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.60

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: rs6803120; hg19: chr3-183602187;