chr1-7962740-CTT-C

Variant names:

• chr1-7962740-CTT-C
• rs370370394
• NM_007262.5:c.-23-5_-23-4delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_007262.5(PARK7):​c.-23-5_-23-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,107,842 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 29)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: PARK7 NM_007262.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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.

• PM2: Variant has high frequency in the AFR (0.0629) population. However there is too low homozygotes in high coverage region: (expected more than 308, got 0).
• BP6: Variant 1-7962740-CTT-C is Benign according to our data. Variant chr1-7962740-CTT-C is described in ClinVar as Benign. ClinVar VariationId is 1229912.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-23-5_-23-4delTT		splice_region intron	N/A	NP_009193.2
	PARK7	NM_001123377.2		c.-23-5_-23-4delTT		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.-23-5_-23-4delTT		splice_region intron	N/A	ENSP00000340278.5	Q99497
	PARK7	ENST00000493678.5	TSL:1	c.-23-5_-23-4delTT		splice_region intron	N/A	ENSP00000418770.1	Q99497
	PARK7	ENST00000872631.1		c.-28_-27delTT		5_prime_UTR	Exon 1 of 6	ENSP00000542690.1

Frequencies

GnomAD3 genomes AF: 0.000530 AC: 61 AN: 115110 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000862

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000268

Gnomad ASJ AF: 0.000363

Gnomad EAS AF: 0.000262

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00225

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000227

Gnomad OTH AF: 0.00133

GnomAD2 exomes AF: 0.0481 AC: 4325 AN: 89970 AF XY: 0.0486

Gnomad AFR exome AF: 0.0790

Gnomad AMR exome AF: 0.0531

Gnomad ASJ exome AF: 0.0317

Gnomad EAS exome AF: 0.0488

Gnomad FIN exome AF: 0.0521

Gnomad NFE exome AF: 0.0475

Gnomad OTH exome AF: 0.0474

GnomAD4 exome AF: 0.0372 AC: 36939 AN: 992744 Hom.: 0 AF XY: 0.0365 AC XY: 18333 AN XY: 502248

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

African (AFR) AF: 0.0657 AC: 1422 AN: 21636

American (AMR) AF: 0.0426 AC: 1127 AN: 26436

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 768 AN: 19764

East Asian (EAS) AF: 0.0416 AC: 1293 AN: 31072

South Asian (SAS) AF: 0.0275 AC: 1734 AN: 63164

European-Finnish (FIN) AF: 0.0417 AC: 1417 AN: 33964

Middle Eastern (MID) AF: 0.0371 AC: 119 AN: 3210

European-Non Finnish (NFE) AF: 0.0364 AC: 27323 AN: 750842

Other (OTH) AF: 0.0407 AC: 1736 AN: 42656

⚠️ 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 AF: 0.000530 AC: 61 AN: 115098 Hom.: 0 Cov.: 29 AF XY: 0.000526 AC XY: 29 AN XY: 55106

African (AFR) AF: 0.000861 AC: 28 AN: 32538

American (AMR) AF: 0.000268 AC: 3 AN: 11212

Ashkenazi Jewish (ASJ) AF: 0.000363 AC: 1 AN: 2752

East Asian (EAS) AF: 0.000263 AC: 1 AN: 3808

South Asian (SAS) AF: 0.00 AC: 0 AN: 3328

European-Finnish (FIN) AF: 0.00225 AC: 14 AN: 6230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000227 AC: 12 AN: 52814

Other (OTH) AF: 0.00133 AC: 2 AN: 1508

Alfa AF: 0.00978 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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: rs370370394; hg19: chr1-8022800;