1-7962858-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007262.5(PARK7):​c.73G>A​(p.Val25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PARK7
NM_007262.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.228
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16552663).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PARK7NM_007262.5 linkuse as main transcriptc.73G>A p.Val25Ile missense_variant 2/7 ENST00000338639.10 NP_009193.2
PARK7NM_001123377.2 linkuse as main transcriptc.73G>A p.Val25Ile missense_variant 2/7 NP_001116849.1
PARK7XM_005263424.4 linkuse as main transcriptc.73G>A p.Val25Ile missense_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.73G>A p.Val25Ile missense_variant 2/71 NM_007262.5 ENSP00000340278 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251482
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461216
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726932
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000227
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal recessive early-onset Parkinson disease 7 Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.28
T;T;T;T;T;T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.86
.;.;.;D;.;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.17
T;T;T;T;T;T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
1.3
L;L;L;.;L;L
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.64
.;N;N;.;N;N
REVEL
Benign
0.15
Sift
Benign
0.19
.;T;T;.;T;T
Sift4G
Benign
0.36
T;T;T;T;T;T
Polyphen
0.0
B;B;B;.;B;B
Vest4
0.11, 0.10, 0.15
MutPred
0.45
Loss of MoRF binding (P = 0.1157);Loss of MoRF binding (P = 0.1157);Loss of MoRF binding (P = 0.1157);Loss of MoRF binding (P = 0.1157);Loss of MoRF binding (P = 0.1157);Loss of MoRF binding (P = 0.1157);
MVP
0.38
MPC
0.10
ClinPred
0.064
T
GERP RS
1.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.22
gMVP
0.48

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

LitVar

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

Other links and lift over

dbSNP: rs781346135; hg19: chr1-8022918; API