3-183868217-C-T

Variant names:

• chr3-183868217-C-T
• rs3749446
• NM_018622.7:c.126-157G>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.126-157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,030 control chromosomes in the GnomAD database, including 37,707 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 (37707 hom., cov: 31)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 22 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 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.126-157G>A		intron	N/A	NP_061092.3
	PARL	NM_001324436.2		c.126-157G>A		intron	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.126-157G>A		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.126-157G>A		intron	N/A	ENSP00000325421.5
	ENSG00000283765	ENST00000639401.1	TSL:5	c.126-157G>A		intron	N/A	ENSP00000491227.1
	PARL	ENST00000311101.9	TSL:1	c.126-157G>A		intron	N/A	ENSP00000310676.5

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106437 AN: 151912 Hom.: 37654 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.701 AC: 106546 AN: 152030 Hom.: 37707 Cov.: 31 AF XY: 0.696 AC XY: 51759 AN XY: 74320

African (AFR) AF: 0.745 AC: 30902 AN: 41452

American (AMR) AF: 0.764 AC: 11671 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2674 AN: 3468

East Asian (EAS) AF: 0.877 AC: 4520 AN: 5156

South Asian (SAS) AF: 0.704 AC: 3395 AN: 4824

European-Finnish (FIN) AF: 0.556 AC: 5879 AN: 10570

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45177 AN: 67980

Other (OTH) AF: 0.733 AC: 1546 AN: 2110

Alfa AF: 0.684 Hom.: 49363

Bravo AF: 0.721

Asia WGS AF: 0.822 AC: 2860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.58
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: rs3749446; hg19: chr3-183586005;