1-7965348-G-T

Position:

• chr1-7965348-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_007262.5(PARK7):​c.115G>T​(p.Ala39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARK7 NM_007262.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.331

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-7965348-G-T is Pathogenic according to our data. Variant chr1-7965348-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 7069.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-7965348-G-T is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.29062006). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARK7	NM_007262.5	c.115G>T	p.Ala39Ser	missense_variant	3/7	ENST00000338639.10	NP_009193.2
PARK7	NM_001123377.2	c.115G>T	p.Ala39Ser	missense_variant	3/7		NP_001116849.1
PARK7	XM_005263424.4	c.115G>T	p.Ala39Ser	missense_variant	3/7		XP_005263481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10	c.115G>T	p.Ala39Ser	missense_variant	3/7	1	NM_007262.5	ENSP00000340278.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Parkinson disease, autosomal recessive early-onset, digenic, PINK1/DJ1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	13
DANN	Benign	0.38
DEOGEN2	Benign	0.20	T;T;T;T;T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.82
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	.;.;.;T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.27	N;N;N;.;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.42	.;N;N;.;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.74	.;T;T;.;T;T
Sift4G	Benign	0.73	T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;B;B
Vest4		0.69, 0.48, 0.29
MutPred		0.79		Gain of glycosylation at A39 (P = 0.0323);Gain of glycosylation at A39 (P = 0.0323);Gain of glycosylation at A39 (P = 0.0323);Gain of glycosylation at A39 (P = 0.0323);Gain of glycosylation at A39 (P = 0.0323);Gain of glycosylation at A39 (P = 0.0323);
MVP		0.99
MPC		0.11
ClinPred		0.026	T
GERP RS		-2.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.18
gMVP		0.33

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: rs137853051; hg19: chr1-8025408;