1-7962863-G-A

Position:

• chr1-7962863-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_007262.5(PARK7):​c.78G>A​(p.Met26Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PARK7 NM_007262.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.66

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.912
• PP5: Variant 1-7962863-G-A is Pathogenic according to our data. Variant chr1-7962863-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 7065.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-7962863-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARK7	NM_007262.5	c.78G>A	p.Met26Ile	missense_variant	2/7	ENST00000338639.10
PARK7	NM_001123377.2	c.78G>A	p.Met26Ile	missense_variant	2/7
PARK7	XM_005263424.4	c.78G>A	p.Met26Ile	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARK7	ENST00000338639.10	c.78G>A	p.Met26Ile	missense_variant	2/7	1	NM_007262.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive early-onset Parkinson disease 7 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T;T;T;T;T
Eigen	Benign	0.014
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.91	D;D;D;D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.2	L;L;L;.;L;L
MutationTaster	Benign	1.0	A;A;A;A;A
PrimateAI	Uncertain	0.73	T
Sift4G	Uncertain	0.026	D;D;D;D;D;D
Polyphen		0.0010	B;B;B;.;B;B
Vest4		0.91, 0.90, 0.82
MutPred		0.91		Loss of catalytic residue at M26 (P = 0.0208);Loss of catalytic residue at M26 (P = 0.0208);Loss of catalytic residue at M26 (P = 0.0208);Loss of catalytic residue at M26 (P = 0.0208);Loss of catalytic residue at M26 (P = 0.0208);Loss of catalytic residue at M26 (P = 0.0208);
MVP		0.98
MPC		0.14
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.79
gMVP		0.89

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

Other links and lift over

dbSNP: rs74315351; hg19: chr1-8022923; COSMIC: COSV58580303; COSMIC: COSV58580303;