1-7962764-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007262.5(PARK7):​c.-22C>T variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,235,092 control chromosomes in the GnomAD database, including 546 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 289 hom., cov: 29)
Exomes 𝑓: 0.0043 ( 257 hom. )

Consequence

PARK7
NM_007262.5 splice_region, 5_prime_UTR

Scores

2
Splicing: ADA: 0.00001403
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.706
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 1-7962764-C-T is Benign according to our data. Variant chr1-7962764-C-T is described in ClinVar as [Benign]. Clinvar id is 298117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PARK7NM_007262.5 linkuse as main transcriptc.-22C>T splice_region_variant, 5_prime_UTR_variant 2/7 ENST00000338639.10 NP_009193.2
PARK7NM_001123377.2 linkuse as main transcriptc.-22C>T splice_region_variant, 5_prime_UTR_variant 2/7 NP_001116849.1
PARK7XM_005263424.4 linkuse as main transcriptc.-22C>T splice_region_variant, 5_prime_UTR_variant 2/7 XP_005263481.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PARK7ENST00000338639.10 linkuse as main transcriptc.-22C>T splice_region_variant, 5_prime_UTR_variant 2/71 NM_007262.5 ENSP00000340278 P1

Frequencies

GnomAD3 genomes
AF:
0.0382
AC:
4959
AN:
129676
Hom.:
288
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.134
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0163
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000489
Gnomad FIN
AF:
0.000483
Gnomad MID
AF:
0.0122
Gnomad NFE
AF:
0.000404
Gnomad OTH
AF:
0.0293
GnomAD3 exomes
AF:
0.00965
AC:
2136
AN:
221380
Hom.:
107
AF XY:
0.00712
AC XY:
856
AN XY:
120244
show subpopulations
Gnomad AFR exome
AF:
0.127
Gnomad AMR exome
AF:
0.00583
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000189
Gnomad FIN exome
AF:
0.000133
Gnomad NFE exome
AF:
0.000331
Gnomad OTH exome
AF:
0.00495
GnomAD4 exome
AF:
0.00429
AC:
4737
AN:
1105350
Hom.:
257
Cov.:
20
AF XY:
0.00369
AC XY:
2070
AN XY:
561640
show subpopulations
Gnomad4 AFR exome
AF:
0.143
Gnomad4 AMR exome
AF:
0.00706
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000295
Gnomad4 FIN exome
AF:
0.000213
Gnomad4 NFE exome
AF:
0.000159
Gnomad4 OTH exome
AF:
0.00966
GnomAD4 genome
AF:
0.0383
AC:
4966
AN:
129742
Hom.:
289
Cov.:
29
AF XY:
0.0385
AC XY:
2374
AN XY:
61644
show subpopulations
Gnomad4 AFR
AF:
0.134
Gnomad4 AMR
AF:
0.0162
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000491
Gnomad4 FIN
AF:
0.000483
Gnomad4 NFE
AF:
0.000404
Gnomad4 OTH
AF:
0.0291
Alfa
AF:
0.00755
Hom.:
28
Bravo
AF:
0.0399

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 17, 2018- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJan 30, 2020- -
Autosomal recessive early-onset Parkinson disease 7 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
9.4
DANN
Benign
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000014
dbscSNV1_RF
Benign
0.0
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11548933; hg19: chr1-8022824; API