chr3-183829177-C-T

Variant names:

• chr3-183829177-C-T
• rs263003
• ENST00000639401.1:c.1028+4315G>A

Variant summary

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

The ENST00000639401.1(ENSG00000283765):​c.1028+4315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 240,300 control chromosomes in the GnomAD database, including 61,412 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 (37448 hom., cov: 31)
  • Exomes 𝑓: 0.73 (23964 hom.)
• Consequence: ENSG00000283765 ENST00000639401.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• Publications: 7 publications found

Genes affected

ENSG00000283765 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000639401.1. 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.*421G>A		downstream_gene	N/A	NP_061092.3
	PARL	NM_001324436.2		c.*421G>A		downstream_gene	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.*421G>A		downstream_gene	N/A	NP_001032728.1	Q9H300-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283765	ENST00000639401.1	TSL:5	c.1028+4315G>A		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	PARL	ENST00000317096.9	TSL:1 MANE Select	c.*421G>A		downstream_gene	N/A	ENSP00000325421.5	Q9H300-1
	PARL	ENST00000311101.9	TSL:1	c.*421G>A		downstream_gene	N/A	ENSP00000310676.5	Q9H300-2

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105856 AN: 151870 Hom.: 37416 Cov.: 31

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.729 AC: 64357 AN: 88312 Hom.: 23964 AF XY: 0.729 AC XY: 33553 AN XY: 46014

African (AFR) AF: 0.617 AC: 2251 AN: 3646

American (AMR) AF: 0.807 AC: 3865 AN: 4790

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 1753 AN: 2154

East Asian (EAS) AF: 0.962 AC: 5327 AN: 5536

South Asian (SAS) AF: 0.702 AC: 7323 AN: 10428

European-Finnish (FIN) AF: 0.633 AC: 2007 AN: 3170

Middle Eastern (MID) AF: 0.792 AC: 263 AN: 332

European-Non Finnish (NFE) AF: 0.712 AC: 38145 AN: 53568

Other (OTH) AF: 0.730 AC: 3423 AN: 4688

GnomAD4 genome AF: 0.697 AC: 105934 AN: 151988 Hom.: 37448 Cov.: 31 AF XY: 0.691 AC XY: 51369 AN XY: 74292

African (AFR) AF: 0.611 AC: 25308 AN: 41418

American (AMR) AF: 0.785 AC: 11984 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2788 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4952 AN: 5178

South Asian (SAS) AF: 0.698 AC: 3361 AN: 4814

European-Finnish (FIN) AF: 0.614 AC: 6472 AN: 10548

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48761 AN: 67976

Other (OTH) AF: 0.731 AC: 1540 AN: 2108

Alfa AF: 0.723 Hom.: 50587

Bravo AF: 0.710

Asia WGS AF: 0.839 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.77
DANN	Benign	0.62
PhyloP100		-0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs263003; hg19: chr3-183546965;