rs2078073

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032409.3(PINK1):c.*672T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 154,648 control chromosomes in the GnomAD database, including 6,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6024 hom., cov: 34)

Exomes 𝑓: 0.29 ( 124 hom. )

Consequence

PINK1
NM_032409.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.463

Publications

8 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 links:

PINK1-AS (HGNC:38872): (PINK1 antisense RNA)

PINK1-AS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-20651363-T-C is Benign according to our data. Variant chr1-20651363-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 295030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINK1	NM_032409.3 link	c.*672T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000321556.5	NP_115785.1	Q9BXM7-1
PINK1-AS	NR_046507.1 link	n.831A>G		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PINK1	ENST00000321556.5 link	c.*672T>C	3_prime_UTR_variant	Exon 8 of 8	1	NM_032409.3	ENSP00000364204.3	Q9BXM7-1
PINK1	ENST00000400490.2 link	n.1511T>C	non_coding_transcript_exon_variant	Exon 4 of 4	2
PINK1-AS	ENST00000451424.1 link	n.831A>G	non_coding_transcript_exon_variant	Exon 1 of 3	2
PINK1	ENST00000492302.1 link	n.*47T>C	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42219

AN:

151986

Hom.:

6021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.287

AC:

729

AN:

2544

Hom.:

124

Cov.:

AF XY:

0.296

AC XY:

372

AN XY:

1256

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.266

AC:

144

AN:

542

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.419

AC:

AN:

148

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.278

AC:

471

AN:

1692

Other (OTH)

AF:

0.289

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.278

AC:

42239

AN:

152104

Hom.:

6024

Cov.:

AF XY:

0.281

AC XY:

20910

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.262

AC:

10892

AN:

41496

American (AMR)

AF:

0.236

AC:

3599

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

683

AN:

3470

East Asian (EAS)

AF:

0.359

AC:

1858

AN:

5180

South Asian (SAS)

AF:

0.381

AC:

1838

AN:

4818

European-Finnish (FIN)

AF:

0.353

AC:

3730

AN:

10568

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18740

AN:

67978

Other (OTH)

AF:

0.266

AC:

562

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1599

3198

4797

6396

7995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.271

Hom.:

4025

Bravo

AF:

0.269

Asia WGS

AF:

0.327

AC:

1134

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital disorder of glycosylation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Parkinson Disease, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive early-onset Parkinson disease 6

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.91

(source)

DANN

Benign

0.66

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over