3-183867753-T-C

Variant names:

• chr3-183867753-T-C
• rs1402000
• NM_018622.7:c.321+112A>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.321+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 789,124 control chromosomes in the GnomAD database, including 192,972 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 0.70 (37767 hom., cov: 30)
  • Exomes 𝑓: 0.69 (155205 hom.)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• Publications: 15 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARL	NM_018622.7	MANE Select	c.321+112A>G		intron	N/A	NP_061092.3
	PARL	NM_001324436.2		c.321+112A>G		intron	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.321+112A>G		intron	N/A	NP_001032728.1	Q9H300-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARL	ENST00000317096.9	TSL:1 MANE Select	c.321+112A>G		intron	N/A	ENSP00000325421.5	Q9H300-1
	ENSG00000283765	ENST00000639401.1	TSL:5	c.321+112A>G		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	PARL	ENST00000311101.9	TSL:1	c.321+112A>G		intron	N/A	ENSP00000310676.5	Q9H300-2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106541 AN: 151788 Hom.: 37715 Cov.: 30

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.728

GnomAD4 exome AF: 0.693 AC: 441442 AN: 637222 Hom.: 155205 AF XY: 0.692 AC XY: 238949 AN XY: 345510

African (AFR) AF: 0.750 AC: 12529 AN: 16712

American (AMR) AF: 0.815 AC: 29949 AN: 36750

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 15123 AN: 19794

East Asian (EAS) AF: 0.899 AC: 32354 AN: 35996

South Asian (SAS) AF: 0.698 AC: 45687 AN: 65452

European-Finnish (FIN) AF: 0.590 AC: 25592 AN: 43402

Middle Eastern (MID) AF: 0.774 AC: 1894 AN: 2446

European-Non Finnish (NFE) AF: 0.665 AC: 255200 AN: 383592

Other (OTH) AF: 0.699 AC: 23114 AN: 33078

GnomAD4 genome AF: 0.702 AC: 106647 AN: 151902 Hom.: 37767 Cov.: 30 AF XY: 0.698 AC XY: 51818 AN XY: 74246

African (AFR) AF: 0.746 AC: 30878 AN: 41410

American (AMR) AF: 0.765 AC: 11671 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2671 AN: 3466

East Asian (EAS) AF: 0.863 AC: 4471 AN: 5180

South Asian (SAS) AF: 0.700 AC: 3366 AN: 4810

European-Finnish (FIN) AF: 0.571 AC: 5999 AN: 10514

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.666 AC: 45262 AN: 67940

Other (OTH) AF: 0.733 AC: 1549 AN: 2114

Alfa AF: 0.690 Hom.: 68967

Bravo AF: 0.722

Asia WGS AF: 0.820 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.7
DANN	Benign	0.59
PhyloP100		-0.39
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: rs1402000; hg19: chr3-183585541; COSMIC: COSV57702989;