3-183884399-T-G

Variant names:

• chr3-183884399-T-G
• rs6803120
• NM_018622.7:c.125+323A>C

Variant summary

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

The NM_018622.7(PARL):​c.125+323A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,128 control chromosomes in the GnomAD database, including 44,227 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 0.76 (44227 hom., cov: 33)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 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.125+323A>C		intron	N/A	NP_061092.3
	PARL	NM_001324436.2		c.125+323A>C		intron	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.125+323A>C		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.125+323A>C		intron	N/A	ENSP00000325421.5	Q9H300-1
	ENSG00000283765	ENST00000639401.1	TSL:5	c.125+323A>C		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	PARL	ENST00000311101.9	TSL:1	c.125+323A>C		intron	N/A	ENSP00000310676.5	Q9H300-2

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115481 AN: 152010 Hom.: 44173 Cov.: 33

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.760 AC: 115591 AN: 152128 Hom.: 44227 Cov.: 33 AF XY: 0.755 AC XY: 56130 AN XY: 74336

African (AFR) AF: 0.798 AC: 33115 AN: 41522

American (AMR) AF: 0.808 AC: 12353 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2848 AN: 3470

East Asian (EAS) AF: 0.955 AC: 4947 AN: 5178

South Asian (SAS) AF: 0.727 AC: 3507 AN: 4822

European-Finnish (FIN) AF: 0.640 AC: 6742 AN: 10540

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49586 AN: 67998

Other (OTH) AF: 0.790 AC: 1668 AN: 2112

Alfa AF: 0.751 Hom.: 23820

Bravo AF: 0.777

Asia WGS AF: 0.856 AC: 2980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.60
PhyloP100		-0.070
PromoterAI		0.027	Neutral
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: rs6803120; hg19: chr3-183602187;