rs387907571

Positions:

chr3-132477995-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2

The NM_015268.4(DNAJC13):c.2564A>G(p.Asn855Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,601,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DNAJC13
NM_015268.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided P:2U:1

Conservation

PhyloP100: 8.71

Variant links:

Genes affected

DNAJC13 (HGNC:30343): (DnaJ heat shock protein family (Hsp40) member C13) This gene encodes a member of the Dnaj protein family whose members act as co-chaperones of a partner heat-shock protein by binding to the latter and stimulating ATP hydrolysis. The encoded protein associates with the heat-shock protein Hsc70 and plays a role in clathrin-mediated endocytosis. It may also be involved in post-endocytic transport mechanisms via its associations with other proteins, including the sorting nexin SNX1. Mutations in this gene are associated with Parkinson's disease. [provided by RefSeq, Jun 2016]

DNAJC13 links:

DNAJC13 (HGNC:):

DNAJC13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNAJC13. . Gene score misZ 2.2836 (greater than the threshold 3.09). Trascript score misZ 3.3776 (greater than threshold 3.09). GenCC has associacion of gene with hereditary late onset Parkinson disease.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.811

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC13	NM_015268.4 linkuse as main transcript	c.2564A>G	p.Asn855Ser	missense_variant	24/56	ENST00000260818.11	NP_056083.3	O75165
DNAJC13	NM_001329126.2 linkuse as main transcript	c.2579A>G	p.Asn860Ser	missense_variant	25/57		NP_001316055.1	B3KN02
DNAJC13	XM_047447819.1 linkuse as main transcript	c.2579A>G	p.Asn860Ser	missense_variant	25/57		XP_047303775.1
DNAJC13	XM_047447820.1 linkuse as main transcript	c.2564A>G	p.Asn855Ser	missense_variant	24/56		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAJC13	ENST00000260818.11 linkuse as main transcript	c.2564A>G	p.Asn855Ser	missense_variant	24/56	1	NM_015268.4	ENSP00000260818.6	O75165
DNAJC13	ENST00000464766.1 linkuse as main transcript	n.401A>G		non_coding_transcript_exon_variant	4/7	5
DNAJC13	ENST00000650455.1 linkuse as main transcript	n.*712A>G		non_coding_transcript_exon_variant	24/57			ENSP00000496825.1	A0A3B3IRM0
DNAJC13	ENST00000650455.1 linkuse as main transcript	n.*712A>G		3_prime_UTR_variant	24/57			ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000418

AC:

AN:

239090

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

129034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000906

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1449748

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

720684

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:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000277

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:2Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Parkinson disease, late-onset

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

CVG, University of British Columbia

- -

Essential tremor

Pathogenic:1

Pathogenic, no assertion criteria provided

research

CVG, University of British Columbia

Jun 03, 2013

- -

Parkinson disease 21

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Apr 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.9

REVEL

Pathogenic

0.70

Sift

Benign

0.11

Sift4G

Benign

0.15

Polyphen

0.99

Vest4

0.89

MutPred

0.56

Gain of disorder (P = 0.0412);

MVP

0.36

MPC

0.54

ClinPred

0.93

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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