Genetic Variant PARK7:c.-23-9_-23-4delTTTTTT (chr1-7962740-CTTTTTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007262.5(PARK7):c.-23-9_-23-4delTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,153,652 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000087 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

PARK7
NM_007262.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PARK7	NM_007262.5 link	c.-23-9_-23-4delTTTTTT	splice_region_variant, intron_variant	Intron 1 of 6	ENST00000338639.10	NP_009193.2	Q99497V9HWC2
PARK7	NM_001123377.2 link	c.-23-9_-23-4delTTTTTT	splice_region_variant, intron_variant	Intron 1 of 6		NP_001116849.1	Q99497V9HWC2
PARK7	XM_005263424.4 link	c.-23-9_-23-4delTTTTTT	splice_region_variant, intron_variant	Intron 1 of 6		XP_005263481.1	Q99497V9HWC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARK7	ENST00000338639.10 link	c.-23-22_-23-17delTTTTTT		intron_variant	Intron 1 of 6	1	NM_007262.5	ENSP00000340278.5		Q99497

Frequencies

GnomAD3 genomes

AF:

0.00000868

AC:

AN:

115208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000262

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:

0.00000867

AC:

AN:

1038444

Hom.:

AF XY:

0.00000951

AC XY:

AN XY:

525734

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000914

Gnomad4 SAS exome

AF:

0.0000151

Gnomad4 FIN exome

AF:

0.0000282

Gnomad4 NFE exome

AF:

0.00000510

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000868

AC:

AN:

115208

Hom.:

Cov.:

AF XY:

0.0000181

AC XY:

AN XY:

55140

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000262

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

1-7962740-CTTTTTTTT-CTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over