3-132447393-C-T

Position:

chr3-132447393-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_015268.4(DNAJC13):c.217C>T(p.Arg73Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000286 in 1,607,982 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 1 hom. )

Consequence

DNAJC13
NM_015268.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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 -3 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.

BS2

High AC in GnomAdExome4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC13	NM_015268.4 linkuse as main transcript	c.217C>T	p.Arg73Cys	missense_variant	4/56	ENST00000260818.11	NP_056083.3	O75165
DNAJC13	NM_001329126.2 linkuse as main transcript	c.217C>T	p.Arg73Cys	missense_variant	4/57		NP_001316055.1	B3KN02
DNAJC13	XM_047447819.1 linkuse as main transcript	c.217C>T	p.Arg73Cys	missense_variant	4/57		XP_047303775.1
DNAJC13	XM_047447820.1 linkuse as main transcript	c.217C>T	p.Arg73Cys	missense_variant	4/56		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAJC13	ENST00000260818.11 linkuse as main transcript	c.217C>T	p.Arg73Cys	missense_variant	4/56	1	NM_015268.4	ENSP00000260818.6	O75165
DNAJC13	ENST00000486798.5 linkuse as main transcript	n.282C>T		non_coding_transcript_exon_variant	4/20	1
DNAJC13	ENST00000650455.1 linkuse as main transcript	n.217C>T		non_coding_transcript_exon_variant	4/57			ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151814

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000935

AC:

AN:

246048

Hom.:

AF XY:

0.0000375

AC XY:

AN XY:

133386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000389

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.0000302

AC:

AN:

1456168

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

724482

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000503

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151814

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74132

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2021

The c.217C>T (p.R73C) alteration is located in exon 4 (coding exon 3) of the DNAJC13 gene. This alteration results from a C to T substitution at nucleotide position 217, causing the arginine (R) at amino acid position 73 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.29

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.81

MutPred

0.44

Loss of MoRF binding (P = 0.0141);

MVP

0.30

MPC

0.51

ClinPred

0.41

GERP RS

5.4

Varity_R

0.49

gMVP

0.79

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