rs11548937

Positions:

• chr1-7969386-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_007262.5(PARK7):​c.234C>T​(p.Gly78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,610,106 control chromosomes in the GnomAD database, including 513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (257 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (256 hom.)
• Consequence: PARK7 NM_007262.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.38

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 1-7969386-C-T is Benign according to our data. Variant chr1-7969386-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 298121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-7969386-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARK7	NM_007262.5	c.234C>T	p.Gly78=	synonymous_variant	4/7	ENST00000338639.10
PARK7	NM_001123377.2	c.234C>T	p.Gly78=	synonymous_variant	4/7
PARK7	XM_005263424.4	c.234C>T	p.Gly78=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARK7	ENST00000338639.10	c.234C>T	p.Gly78=	synonymous_variant	4/7	1	NM_007262.5	P1

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 4842 AN: 150542 Hom.: 257 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00973

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00231

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.000591

Gnomad OTH AF: 0.0256

GnomAD3 exomes AF: 0.00854 AC: 2147 AN: 251288 Hom.: 110 AF XY: 0.00639 AC XY: 868 AN XY: 135852

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.00480

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00291

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000493

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00357 AC: 5210 AN: 1459454 Hom.: 256 Cov.: 31 AF XY: 0.00326 AC XY: 2370 AN XY: 726224

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.00526

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00310

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000295

Gnomad4 OTH exome AF: 0.00805

GnomAD4 genome AF: 0.0323 AC: 4860 AN: 150652 Hom.: 257 Cov.: 32 AF XY: 0.0316 AC XY: 2321 AN XY: 73370

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.00972

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00231

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000591

Gnomad4 OTH AF: 0.0254

Alfa AF: 0.0212 Hom.: 63

Bravo AF: 0.0369

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.000474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 30, 2018	This variant is associated with the following publications: (PMID: 27884173, 12953260, 20981092) -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 18, 2018	- -

Parkinson Disease, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Autosomal recessive early-onset Parkinson disease 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	4.0
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11548937; hg19: chr1-8029446;