1-7962740-CTTTTTTTT-CTTTTTTTTTTT

Variant names:

• chr1-7962740-C-CTTT
• rs370370394
• NM_007262.5:c.-23-6_-23-4dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_007262.5(PARK7):​c.-23-6_-23-4dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PARK7 NM_007262.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

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.-23-6_-23-4dupTTT		splice_region intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.-23-6_-23-4dupTTT		splice_region 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.-23-6_-23-4dupTTT		splice_region intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-23-6_-23-4dupTTT		splice_region intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000872631.1		c.-29_-27dupTTT		5_prime_UTR	Exon 1 of 6	ENSP00000542690.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 115200 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000412 AC: 427 AN: 1037052 Hom.: 0 Cov.: 0 AF XY: 0.000404 AC XY: 212 AN XY: 525066

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000222 AC: 5 AN: 22498

American (AMR) AF: 0.000323 AC: 9 AN: 27852

Ashkenazi Jewish (ASJ) AF: 0.000389 AC: 8 AN: 20578

East Asian (EAS) AF: 0.000274 AC: 9 AN: 32798

South Asian (SAS) AF: 0.000440 AC: 29 AN: 65984

European-Finnish (FIN) AF: 0.000424 AC: 15 AN: 35418

Middle Eastern (MID) AF: 0.000592 AC: 2 AN: 3378

European-Non Finnish (NFE) AF: 0.000418 AC: 328 AN: 783946

Other (OTH) AF: 0.000493 AC: 22 AN: 44600

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 115200 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 55138

African (AFR) AF: 0.00 AC: 0 AN: 32508

American (AMR) AF: 0.00 AC: 0 AN: 11222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2752

East Asian (EAS) AF: 0.00 AC: 0 AN: 3822

South Asian (SAS) AF: 0.00 AC: 0 AN: 3346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52860

Other (OTH) AF: 0.00 AC: 0 AN: 1506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370370394; hg19: chr1-8022800;