NM_018622.7:c.511+3941G>A

Variant names:

• chr3-183858812-C-T
• rs6775202
• NM_018622.7:c.511+3941G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018622.7(PARL):​c.511+3941G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,688 control chromosomes in the GnomAD database, including 17,993 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 0.48 (17993 hom., cov: 30)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7	c.511+3941G>A		intron_variant	Intron 4 of 9	ENST00000317096.9	NP_061092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9	c.511+3941G>A		intron_variant	Intron 4 of 9	1	NM_018622.7	ENSP00000325421.5
ENSG00000283765	ENST00000639401.1	c.511+3941G>A		intron_variant	Intron 4 of 10	5		ENSP00000491227.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73244 AN: 151568 Hom.: 17985 Cov.: 30

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.483 AC: 73270 AN: 151688 Hom.: 17993 Cov.: 30 AF XY: 0.476 AC XY: 35257 AN XY: 74130

African (AFR) AF: 0.533 AC: 22013 AN: 41284

American (AMR) AF: 0.503 AC: 7659 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1919 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2163 AN: 5136

South Asian (SAS) AF: 0.417 AC: 2006 AN: 4814

European-Finnish (FIN) AF: 0.324 AC: 3414 AN: 10524

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32622 AN: 67920

Other (OTH) AF: 0.502 AC: 1057 AN: 2106

Alfa AF: 0.482 Hom.: 12866

Bravo AF: 0.504

Asia WGS AF: 0.419 AC: 1461 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	2.5
DANN	Benign	0.52
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6775202; hg19: chr3-183576600;