rs2305666

Variant names:

• chr3-183833945-A-C
• rs2305666
• NM_018622.7:c.829-120T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-183833945-A-C
• chr3-183833945-A-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.829-120T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 731,038 control chromosomes in the GnomAD database, including 14,470 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 0.19 (3014 hom., cov: 32)
  • Exomes 𝑓: 0.19 (11456 hom.)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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.829-120T>G		intron	N/A	NP_061092.3
	PARL	NM_001324436.2		c.829-356T>G		intron	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.679-120T>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.829-120T>G		intron	N/A	ENSP00000325421.5	Q9H300-1
	ENSG00000283765	ENST00000639401.1	TSL:5	c.829-120T>G		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	PARL	ENST00000311101.9	TSL:1	c.679-120T>G		intron	N/A	ENSP00000310676.5	Q9H300-2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29159 AN: 152098 Hom.: 2993 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.187 AC: 107980 AN: 578822 Hom.: 11456 AF XY: 0.184 AC XY: 57309 AN XY: 311590

African (AFR) AF: 0.197 AC: 3177 AN: 16142

American (AMR) AF: 0.246 AC: 8492 AN: 34526

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 3844 AN: 19628

East Asian (EAS) AF: 0.420 AC: 13753 AN: 32782

South Asian (SAS) AF: 0.155 AC: 9644 AN: 62404

European-Finnish (FIN) AF: 0.161 AC: 7907 AN: 48970

Middle Eastern (MID) AF: 0.160 AC: 610 AN: 3812

European-Non Finnish (NFE) AF: 0.165 AC: 54490 AN: 329610

Other (OTH) AF: 0.196 AC: 6063 AN: 30948

GnomAD4 genome AF: 0.192 AC: 29216 AN: 152216 Hom.: 3014 Cov.: 32 AF XY: 0.191 AC XY: 14219 AN XY: 74420

African (AFR) AF: 0.195 AC: 8091 AN: 41540

American (AMR) AF: 0.236 AC: 3608 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 696 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2214 AN: 5166

South Asian (SAS) AF: 0.153 AC: 739 AN: 4824

European-Finnish (FIN) AF: 0.172 AC: 1823 AN: 10598

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11361 AN: 67996

Other (OTH) AF: 0.193 AC: 407 AN: 2112

Alfa AF: 0.184 Hom.: 1375

Bravo AF: 0.198

Asia WGS AF: 0.304 AC: 1056 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		0.67
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: rs2305666; hg19: chr3-183551733; COSMIC: COSV107320257;