1-7961913-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007262.5(PARK7):c.-24+120G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,330 control chromosomes in the GnomAD database, including 2,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2900 hom., cov: 33)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-7961913-G-T is Benign according to our data. Variant chr1-7961913-G-T is described in ClinVar as [Benign]. Clinvar id is 1243450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARK7	NM_007262.5	c.-24+120G>T		intron_variant		ENST00000338639.10
PARK7	XM_005263424.4	c.-192G>T		5_prime_UTR_variant	1/7
PARK7	NM_001123377.2	c.-24+178G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARK7	ENST00000338639.10	c.-24+120G>T		intron_variant		1	NM_007262.5	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28030 AN: 152054 Hom.: 2892 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.131 AC: 21 AN: 160 Hom.: 1 Cov.: 0 AF XY: 0.136 AC XY: 15 AN XY: 110

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.184 AC: 28061 AN: 152170 Hom.: 2900 Cov.: 33 AF XY: 0.184 AC XY: 13728 AN XY: 74412

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0628

Gnomad4 SAS AF: 0.0957

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.159

Alfa AF: 0.147 Hom.: 1599

Bravo AF: 0.178

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.3
Dann	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs35675666; hg19: chr1-8021973;