NM_015268.4:c.2564A>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PM5PP3

The NM_015268.4(DNAJC13):c.2564A>C(p.Asn855Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N855S) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNAJC13
NM_015268.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.71

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hereditary late onset Parkinson disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAJC13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr3-132477995-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 56171.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC13	NM_015268.4 link	c.2564A>C	p.Asn855Thr	missense_variant	Exon 24 of 56	ENST00000260818.11	NP_056083.3	O75165
DNAJC13	NM_001329126.2 link	c.2579A>C	p.Asn860Thr	missense_variant	Exon 25 of 57		NP_001316055.1	B3KN02
DNAJC13	XM_047447819.1 link	c.2579A>C	p.Asn860Thr	missense_variant	Exon 25 of 57		XP_047303775.1
DNAJC13	XM_047447820.1 link	c.2564A>C	p.Asn855Thr	missense_variant	Exon 24 of 56		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAJC13	ENST00000260818.11 link	c.2564A>C	p.Asn855Thr	missense_variant	Exon 24 of 56	1	NM_015268.4	ENSP00000260818.6	O75165
DNAJC13	ENST00000464766.1 link	n.401A>C		non_coding_transcript_exon_variant	Exon 4 of 7	5
DNAJC13	ENST00000650455.1 link	n.*712A>C		non_coding_transcript_exon_variant	Exon 24 of 57			ENSP00000496825.1	A0A3B3IRM0
DNAJC13	ENST00000650455.1 link	n.*712A>C		3_prime_UTR_variant	Exon 24 of 57			ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720684

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32384

American (AMR)

AF:

0.00

AC:

AN:

41750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25596

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39558

South Asian (SAS)

AF:

0.00

AC:

AN:

82748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109040

Other (OTH)

AF:

0.00

AC:

AN:

59810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

8.7

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.47

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.84

MutPred

0.55

Gain of glycosylation at S850 (P = 0.0496);

MVP

0.26

MPC

0.71

ClinPred

0.99

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.57

Mutation Taster

=27/73

disease causing

(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