Genetic Variant PINK1:c.675+820T>C (chr1-20638949-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032409.3(PINK1):c.675+820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,262 control chromosomes in the GnomAD database, including 5,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 5559 hom., cov: 33)

Exomes 𝑓: 0.15 ( 3 hom. )

Consequence

PINK1
NM_032409.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.802

Publications

12 publications found

Variant links:

Genes affected

PINK1 (HGNC:14581): (PTEN induced kinase 1) This gene encodes a serine/threonine protein kinase that localizes to mitochondria. It is thought to protect cells from stress-induced mitochondrial dysfunction. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson disease. [provided by RefSeq, Jul 2008]

PINK1 Gene-Disease associations (from GenCC):

autosomal recessive early-onset Parkinson disease 6
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Parkinson disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PINK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINK1	NM_032409.3 link	c.675+820T>C		intron_variant	Intron 2 of 7	ENST00000321556.5	NP_115785.1	Q9BXM7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINK1	ENST00000321556.5 link	c.675+820T>C		intron_variant	Intron 2 of 7	1	NM_032409.3	ENSP00000364204.3		Q9BXM7-1
PINK1	ENST00000492302.1 link	n.821T>C		non_coding_transcript_exon_variant	Exon 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40362

AN:

152020

Hom.:

5554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.148

AC:

AN:

122

Hom.:

Cov.:

AF XY:

0.172

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.155

AC:

AN:

116

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.265

AC:

40379

AN:

152140

Hom.:

5559

Cov.:

AF XY:

0.270

AC XY:

20069

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.224

AC:

9305

AN:

41492

American (AMR)

AF:

0.229

AC:

3501

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

683

AN:

3472

East Asian (EAS)

AF:

0.348

AC:

1800

AN:

5174

South Asian (SAS)

AF:

0.373

AC:

1798

AN:

4824

European-Finnish (FIN)

AF:

0.352

AC:

3720

AN:

10580

Middle Eastern (MID)

AF:

0.195

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.275

AC:

18705

AN:

67996

Other (OTH)

AF:

0.252

AC:

532

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1498

2995

4493

5990

7488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.266

Hom.:

9073

Bravo

AF:

0.255

Asia WGS

AF:

0.308

AC:

1070

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.4

(source)

DANN

Benign

0.78

PhyloP100

-0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over