chr3-132447458-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_015268.4(DNAJC13):c.282T>G(p.Leu94Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,574,692 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 18 hom., cov: 32)

Exomes 𝑓: 0.016 ( 208 hom. )

Consequence

DNAJC13
NM_015268.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:4

Conservation

PhyloP100: 1.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 3-132447458-T-G is Benign according to our data. Variant chr3-132447458-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1210070.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-132447458-T-G is described in Lovd as [Likely_benign]. Variant chr3-132447458-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.24 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0114 (1738/152224) while in subpopulation NFE AF= 0.0167 (1136/67976). AF 95% confidence interval is 0.0159. There are 18 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1738 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC13	NM_015268.4 link	c.282T>G	p.Leu94Leu	synonymous_variant	Exon 4 of 56	ENST00000260818.11	NP_056083.3	O75165
DNAJC13	NM_001329126.2 link	c.282T>G	p.Leu94Leu	synonymous_variant	Exon 4 of 57		NP_001316055.1	B3KN02
DNAJC13	XM_047447819.1 link	c.282T>G	p.Leu94Leu	synonymous_variant	Exon 4 of 57		XP_047303775.1
DNAJC13	XM_047447820.1 link	c.282T>G	p.Leu94Leu	synonymous_variant	Exon 4 of 56		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAJC13	ENST00000260818.11 link	c.282T>G	p.Leu94Leu	synonymous_variant	Exon 4 of 56	1	NM_015268.4	ENSP00000260818.6	O75165
DNAJC13	ENST00000486798.5 link	n.347T>G		non_coding_transcript_exon_variant	Exon 4 of 20	1
DNAJC13	ENST00000650455.1 link	n.282T>G		non_coding_transcript_exon_variant	Exon 4 of 57			ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1737

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00963

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.00953

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0167

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0119

AC:

2484

AN:

208172

Hom.:

AF XY:

0.0121

AC XY:

1384

AN XY:

113938

show subpopulations

Gnomad AFR exome

AF:

0.00335

Gnomad AMR exome

AF:

0.00822

Gnomad ASJ exome

AF:

0.0335

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00899

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0128

GnomAD4 exome

AF:

0.0157

AC:

22330

AN:

1422468

Hom.:

208

Cov.:

AF XY:

0.0154

AC XY:

10914

AN XY:

707294

show subpopulations

Gnomad4 AFR exome

AF:

0.00249

Gnomad4 AMR exome

AF:

0.00760

Gnomad4 ASJ exome

AF:

0.0314

Gnomad4 EAS exome

AF:

0.0000520

Gnomad4 SAS exome

AF:

0.00825

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0138

GnomAD4 genome

AF:

0.0114

AC:

1738

AN:

152224

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

842

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00419

Gnomad4 AMR

AF:

0.00961

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.00953

Gnomad4 NFE

AF:

0.0167

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0164

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00318

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

DNAJC13-related disorder

Benign:1

Mar 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.4

DANN

Benign

0.78

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