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

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

Gnomad4 AMR exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.155

GnomAD4 genome

AF:

0.265

AC:

40379

AN:

152140

Hom.:

5559

Cov.:

AF XY:

0.270

AC XY:

20069

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.373

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.268

Hom.:

7323

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

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

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

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