Variant rs1801582 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_004562.3(PRKN):c.1138G>T(p.Val380Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Benignin Lovd.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRKN
NM_004562.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.121

Variant links:

Genes affected

PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

PRKN links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077436).

BP6

Variant 6-161386823-C-A is Benign according to our data. Variant chr6-161386823-C-A is described in ClinVar as [Benign]. Clinvar id is 1622630.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3 linkuse as main transcript	c.1138G>T	p.Val380Leu	missense_variant	10/12	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6 linkuse as main transcript	c.1138G>T	p.Val380Leu	missense_variant	10/12	1	NM_004562.3	ENSP00000355865	P1	O60260-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.52

DANN

Benign

0.21

DEOGEN2

Benign

0.068

T;.;.;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.059

T;T;T;T;.;T

M_CAP

Benign

0.077

MetaRNN

Benign

0.077

T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.090

N;N;N;.;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.38

T;T;T;.;T;T

Sift4G

Benign

0.81

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.030

MutPred

0.099

Gain of helix (P = 0.0199);.;.;.;.;.;

MVP

0.71

MPC

0.055

ClinPred

0.050

GERP RS

2.7

Varity_R

0.14

gMVP

0.27

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over