1-7969386-C-T

Variant names:

• chr1-7969386-C-T
• rs11548937
• NM_007262.5:c.234C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_007262.5(PARK7):​c.234C>T​(p.Gly78Gly) 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:8
• Conservation: PhyloP100: -1.38
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• Parkinson disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive early-onset Parkinson disease 7

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 298121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007262.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARK7	NM_007262.5	MANE Select	c.234C>T	p.Gly78Gly	synonymous	Exon 4 of 7	NP_009193.2
	PARK7	NM_001123377.2		c.234C>T	p.Gly78Gly	synonymous	Exon 4 of 7	NP_001116849.1	Q99497

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARK7	ENST00000338639.10	TSL:1 MANE Select	c.234C>T	p.Gly78Gly	synonymous	Exon 4 of 7	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.234C>T	p.Gly78Gly	synonymous	Exon 4 of 7	ENSP00000418770.1	Q99497
	PARK7	ENST00000923305.1		c.234C>T	p.Gly78Gly	synonymous	Exon 4 of 8	ENSP00000593364.1

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

GnomAD2 exomes AF: 0.00854 AC: 2147 AN: 251288 AF XY: 0.00639

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 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

African (AFR) AF: 0.115 AC: 3849 AN: 33400

American (AMR) AF: 0.00526 AC: 235 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39644

South Asian (SAS) AF: 0.00310 AC: 267 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00801 AC: 46 AN: 5746

European-Non Finnish (NFE) AF: 0.000295 AC: 327 AN: 1110128

Other (OTH) AF: 0.00805 AC: 485 AN: 60272

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

African (AFR) AF: 0.112 AC: 4608 AN: 41146

American (AMR) AF: 0.00972 AC: 146 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00231 AC: 11 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10116

Middle Eastern (MID) AF: 0.00709 AC: 2 AN: 282

European-Non Finnish (NFE) AF: 0.000591 AC: 40 AN: 67732

Other (OTH) AF: 0.0254 AC: 53 AN: 2090

Alfa AF: 0.0211 Hom.: 63

Bravo AF: 0.0369

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Autosomal recessive early-onset Parkinson disease 7 (1)
-	-	1	Parkinson Disease, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs11548937; hg19: chr1-8029446;