dbSNP rs3811725: PARL:c.512-162T>G (chr3-183844488-A-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.512-162T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 621,298 control chromosomes in the GnomAD database, including 65,056 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 0.42 ( 14020 hom., cov: 32)

Exomes 𝑓: 0.46 ( 51036 hom. )

Consequence

PARL
NM_018622.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.640

Publications

15 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:

Genome browser will be placed here

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=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7 link	c.512-162T>G		intron_variant	Intron 4 of 9	ENST00000317096.9	NP_061092.3	Q9H300-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9 link	c.512-162T>G		intron_variant	Intron 4 of 9	1	NM_018622.7	ENSP00000325421.5		Q9H300-1
ENSG00000283765	ENST00000639401.1 link	c.512-162T>G		intron_variant	Intron 4 of 10	5		ENSP00000491227.1		A0A1W2PP11

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64120

AN:

151948

Hom.:

14020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.462

AC:

216643

AN:

469232

Hom.:

51036

Cov.:

AF XY:

0.461

AC XY:

116192

AN XY:

251952

show subpopulations

African (AFR)

AF:

0.316

AC:

4028

AN:

12746

American (AMR)

AF:

0.511

AC:

11415

AN:

22334

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

7983

AN:

14698

East Asian (EAS)

AF:

0.456

AC:

13654

AN:

29966

South Asian (SAS)

AF:

0.421

AC:

19620

AN:

46638

European-Finnish (FIN)

AF:

0.347

AC:

12944

AN:

37256

Middle Eastern (MID)

AF:

0.570

AC:

1242

AN:

2178

European-Non Finnish (NFE)

AF:

0.482

AC:

133694

AN:

277362

Other (OTH)

AF:

0.463

AC:

12063

AN:

26054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5449

10898

16348

21797

27246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.422

AC:

64125

AN:

152066

Hom.:

14020

Cov.:

AF XY:

0.416

AC XY:

30903

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.314

AC:

13031

AN:

41454

American (AMR)

AF:

0.483

AC:

7382

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

1921

AN:

3470

East Asian (EAS)

AF:

0.420

AC:

2172

AN:

5170

South Asian (SAS)

AF:

0.419

AC:

2019

AN:

4820

European-Finnish (FIN)

AF:

0.324

AC:

3431

AN:

10592

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.482

AC:

32785

AN:

67970

Other (OTH)

AF:

0.449

AC:

949

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1817

3634

5450

7267

9084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.472

Hom.:

55268

Bravo

AF:

0.434

Asia WGS

AF:

0.406

AC:

1413

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.74

(source)

DANN

Benign

0.83

PhyloP100

-0.64

PromoterAI

0.013

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over