NM_007262.5:c.293G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007262.5(PARK7):c.293G>A(p.Arg98Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00932 in 1,614,132 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R98W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0071 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 99 hom. )

Consequence

PARK7
NM_007262.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 5.37

Publications

52 publications found

Variant links:

Genes affected

PARK7 (HGNC:16369): (Parkinsonism associated deglycase) The product of this gene belongs to the peptidase C56 family of proteins. It acts as a positive regulator of androgen receptor-dependent transcription. It may also function as a redox-sensitive chaperone, as a sensor for oxidative stress, and it apparently protects neurons against oxidative stress and cell death. Defects in this gene are the cause of autosomal recessive early-onset Parkinson disease 7. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

PARK7 Gene-Disease associations (from GenCC):

Parkinson disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive early-onset Parkinson disease 7
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PARK7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007415414).

BP6

Variant 1-7970934-G-A is Benign according to our data. Variant chr1-7970934-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 465831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00715 (1088/152266) while in subpopulation NFE AF = 0.0114 (774/68014). AF 95% confidence interval is 0.0107. There are 5 homozygotes in GnomAd4. There are 483 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007262.5. 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
	PARK7	NM_007262.5	MANE Select	c.293G>A	p.Arg98Gln	missense	Exon 5 of 7	NP_009193.2
	PARK7	NM_001123377.2		c.293G>A	p.Arg98Gln	missense	Exon 5 of 7	NP_001116849.1	Q99497

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PARK7	ENST00000338639.10	TSL:1 MANE Select	c.293G>A	p.Arg98Gln	missense	Exon 5 of 7	ENSP00000340278.5	Q99497
PARK7	ENST00000493678.5	TSL:1	c.293G>A	p.Arg98Gln	missense	Exon 5 of 7	ENSP00000418770.1	Q99497
PARK7	ENST00000923305.1		c.293G>A	p.Arg98Gln	missense	Exon 5 of 8	ENSP00000593364.1

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

1088

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00863

GnomAD2 exomes

AF:

0.00789

AC:

1984

AN:

251484

AF XY:

0.00853

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00598

Gnomad ASJ exome

AF:

0.00982

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00879

GnomAD4 exome

AF:

0.00955

AC:

13957

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00970

AC XY:

7051

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

33480

American (AMR)

AF:

0.00606

AC:

271

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0111

AC:

289

AN:

26134

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.0122

AC:

1055

AN:

86256

European-Finnish (FIN)

AF:

0.00127

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0189

AC:

109

AN:

5768

European-Non Finnish (NFE)

AF:

0.0104

AC:

11537

AN:

1111994

Other (OTH)

AF:

0.00940

AC:

568

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

786

1572

2358

3144

3930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.00715

AC:

1088

AN:

152266

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

483

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

41554

American (AMR)

AF:

0.00660

AC:

101

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00894

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0108

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000848

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

774

AN:

68014

Other (OTH)

AF:

0.00854

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00931

Hom.:

Bravo

AF:

0.00706

TwinsUK

AF:

0.0124

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.00815

AC:

989

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0150

EpiControl

AF:

0.0137

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (6)

Autosomal recessive early-onset Parkinson disease 7 (3)

not specified (1)

PARK7-related disorder (1)

Renal cysts and diabetes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.21

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.56

PhyloP100

5.4

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.23

REVEL

Benign

0.20

Sift

Benign

0.51

Sift4G

Benign

0.62

Polyphen

0.0050

Vest4

0.40

MVP

0.60

MPC

0.15

ClinPred

0.0021

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.66

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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