NM_007262.5:c.-23-70T>G

Variant names:

• chr1-7962693-T-G
• rs17031860
• NM_007262.5:c.-23-70T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007262.5(PARK7):​c.-23-70T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,015,436 control chromosomes in the GnomAD database, including 887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (560 hom., cov: 31)
  • Exomes 𝑓: 0.0049 (327 hom.)
• Consequence: PARK7 NM_007262.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.311
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-7962693-T-G is Benign according to our data. Variant chr1-7962693-T-G is described in ClinVar as Benign. ClinVar VariationId is 1296707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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.-23-70T>G		intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.-23-70T>G		intron	N/A	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.-23-70T>G		intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-23-70T>G		intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000872631.1		c.-93T>G		5_prime_UTR	Exon 1 of 6	ENSP00000542690.1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 6983 AN: 148700 Hom.: 559 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000496

Gnomad OTH AF: 0.0367

GnomAD4 exome AF: 0.00494 AC: 4282 AN: 866624 Hom.: 327 AF XY: 0.00430 AC XY: 1926 AN XY: 447488

African (AFR) AF: 0.162 AC: 3221 AN: 19892

American (AMR) AF: 0.00857 AC: 255 AN: 29764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21096

East Asian (EAS) AF: 0.0000593 AC: 2 AN: 33746

South Asian (SAS) AF: 0.00329 AC: 208 AN: 63306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36552

Middle Eastern (MID) AF: 0.00713 AC: 21 AN: 2944

European-Non Finnish (NFE) AF: 0.000207 AC: 128 AN: 619214

Other (OTH) AF: 0.0111 AC: 447 AN: 40110

GnomAD4 genome AF: 0.0471 AC: 7002 AN: 148812 Hom.: 560 Cov.: 31 AF XY: 0.0454 AC XY: 3300 AN XY: 72672

African (AFR) AF: 0.163 AC: 6649 AN: 40794

American (AMR) AF: 0.0155 AC: 233 AN: 15002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

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

South Asian (SAS) AF: 0.00210 AC: 10 AN: 4754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9884

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000496 AC: 33 AN: 66538

Other (OTH) AF: 0.0363 AC: 75 AN: 2066

Alfa AF: 0.0177 Hom.: 189

Bravo AF: 0.0541

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.66
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17031860; hg19: chr1-8022753;