Genetic Variant PARL:c.758-153C>G (chr3-183840793-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018622.7(PARL):c.758-153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 150,226 control chromosomes in the GnomAD database, including 7,319 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 0.29 ( 7306 hom., cov: 29)

Exomes 𝑓: 0.15 ( 13 hom. )

Consequence

PARL
NM_018622.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.05

Publications

4 publications found

Variant links:

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]

PARL links:

ENSG00000283765 (HGNC:):

ENSG00000283765 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PARL	NM_018622.7	MANE Select	c.758-153C>G	intron	N/A	NP_061092.3
PARL	NM_001324436.2		c.758-153C>G	intron	N/A	NP_001311365.1
PARL	NM_001037639.3		c.608-153C>G	intron	N/A	NP_001032728.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PARL	ENST00000317096.9	TSL:1 MANE Select	c.758-153C>G	intron	N/A	ENSP00000325421.5
ENSG00000283765	ENST00000639401.1	TSL:5	c.758-153C>G	intron	N/A	ENSP00000491227.1
PARL	ENST00000311101.9	TSL:1	c.608-153C>G	intron	N/A	ENSP00000310676.5

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43098

AN:

149318

Hom.:

7265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.149

AC:

118

AN:

794

Hom.:

AF XY:

0.161

AC XY:

AN XY:

416

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.125

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.140

AC:

102

AN:

728

Other (OTH)

AF:

0.211

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.289

AC:

43206

AN:

149432

Hom.:

7306

Cov.:

AF XY:

0.291

AC XY:

21125

AN XY:

72656

show subpopulations

African (AFR)

AF:

0.462

AC:

18787

AN:

40674

American (AMR)

AF:

0.289

AC:

4278

AN:

14808

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

755

AN:

3462

East Asian (EAS)

AF:

0.460

AC:

2338

AN:

5082

South Asian (SAS)

AF:

0.255

AC:

1211

AN:

4748

European-Finnish (FIN)

AF:

0.237

AC:

2334

AN:

9836

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.186

AC:

12534

AN:

67548

Other (OTH)

AF:

0.287

AC:

596

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1357

2714

4070

5427

6784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.113

Hom.:

185

Bravo

AF:

0.298

Asia WGS

AF:

0.404

AC:

1404

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.46

(source)

DANN

Benign

0.36

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over