NM_018622.7:c.758-153C>G

Variant names:

• chr3-183840793-G-C
• rs12636826
• NM_018622.7:c.758-153C>G

Variant summary

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

The NM_018622.7(PARL):​c.758-153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 150,226 control chromosomes in the GnomAD database, including 7,319 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 0.29 (7306 hom., cov: 29)
  • Exomes 𝑓: 0.15 (13 hom.)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 4 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018622.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARL	NM_018622.7	MANE Select	c.758-153C>G		intron	N/A	NP_061092.3
	PARL	NM_001324436.2		c.758-153C>G		intron	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.608-153C>G		intron	N/A	NP_001032728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARL	ENST00000317096.9	TSL:1 MANE Select	c.758-153C>G		intron	N/A	ENSP00000325421.5
	ENSG00000283765	ENST00000639401.1	TSL:5	c.758-153C>G		intron	N/A	ENSP00000491227.1
	PARL	ENST00000311101.9	TSL:1	c.608-153C>G		intron	N/A	ENSP00000310676.5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43098 AN: 149318 Hom.: 7265 Cov.: 29

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.149 AC: 118 AN: 794 Hom.: 13 AF XY: 0.161 AC XY: 67 AN XY: 416

African (AFR) AF: 0.400 AC: 4 AN: 10

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.125 AC: 1 AN: 8

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.140 AC: 102 AN: 728

Other (OTH) AF: 0.211 AC: 8 AN: 38

GnomAD4 genome AF: 0.289 AC: 43206 AN: 149432 Hom.: 7306 Cov.: 29 AF XY: 0.291 AC XY: 21125 AN XY: 72656

African (AFR) AF: 0.462 AC: 18787 AN: 40674

American (AMR) AF: 0.289 AC: 4278 AN: 14808

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3462

East Asian (EAS) AF: 0.460 AC: 2338 AN: 5082

South Asian (SAS) AF: 0.255 AC: 1211 AN: 4748

European-Finnish (FIN) AF: 0.237 AC: 2334 AN: 9836

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12534 AN: 67548

Other (OTH) AF: 0.287 AC: 596 AN: 2074

Alfa AF: 0.113 Hom.: 185

Bravo AF: 0.298

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.36
PhyloP100		-2.1
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: rs12636826; hg19: chr3-183558581;