chr1-65384204-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001256864.2(DNAJC6):c.678G>A(p.Ala226Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,516,340 control chromosomes in the GnomAD database, including 483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 30 hom., cov: 32)

Exomes 𝑓: 0.024 ( 453 hom. )

Consequence

DNAJC6
NM_001256864.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.199

Publications

2 publications found

Variant links:

Genes affected

DNAJC6 (HGNC:15469): (DnaJ heat shock protein family (Hsp40) member C6) DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus, a glycine/phenylalanine (G/F)-rich region, and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

DNAJC6 Gene-Disease associations (from GenCC):

juvenile onset Parkinson disease 19A
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
atypical juvenile parkinsonism
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNAJC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-65384204-G-A is Benign according to our data. Variant chr1-65384204-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.199 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.018 (2733/152158) while in subpopulation NFE AF = 0.027 (1837/67996). AF 95% confidence interval is 0.026. There are 30 homozygotes in GnomAd4. There are 1314 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DNAJC6	NM_001256864.2 link	c.678G>A	p.Ala226Ala	synonymous_variant	Exon 6 of 19	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4 link	c.507G>A	p.Ala169Ala	synonymous_variant	Exon 6 of 19		NP_055602.1
DNAJC6	NM_001256865.2 link	c.468G>A	p.Ala156Ala	synonymous_variant	Exon 7 of 20		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5 link	c.678G>A	p.Ala226Ala	synonymous_variant	Exon 6 of 19	1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2736

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00444

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00499

Gnomad FIN

AF:

0.0246

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0230

GnomAD2 exomes

AF:

0.0203

AC:

3818

AN:

188090

AF XY:

0.0206

show subpopulations

Gnomad AFR exome

AF:

0.00424

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.0294

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0236

AC:

32240

AN:

1364182

Hom.:

453

Cov.:

AF XY:

0.0231

AC XY:

15589

AN XY:

675412

show subpopulations

African (AFR)

AF:

0.00454

AC:

131

AN:

28824

American (AMR)

AF:

0.0137

AC:

410

AN:

29924

Ashkenazi Jewish (ASJ)

AF:

0.0183

AC:

423

AN:

23168

East Asian (EAS)

AF:

0.0000299

AC:

AN:

33450

South Asian (SAS)

AF:

0.00670

AC:

469

AN:

69982

European-Finnish (FIN)

AF:

0.0235

AC:

1215

AN:

51612

Middle Eastern (MID)

AF:

0.0398

AC:

217

AN:

5450

European-Non Finnish (NFE)

AF:

0.0263

AC:

28072

AN:

1065668

Other (OTH)

AF:

0.0232

AC:

1302

AN:

56104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

1570

3140

4711

6281

7851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1076

2152

3228

4304

5380

<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

AF:

0.0180

AC:

2733

AN:

152158

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1314

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00446

AC:

185

AN:

41526

American (AMR)

AF:

0.0190

AC:

290

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5158

South Asian (SAS)

AF:

0.00457

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0246

AC:

261

AN:

10598

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0270

AC:

1837

AN:

67996

Other (OTH)

AF:

0.0227

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

141

282

422

563

704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0233

Hom.:

102

Bravo

AF:

0.0174

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Oct 06, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Juvenile onset Parkinson disease 19A

Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.8

(source)

DANN

Benign

0.72

PhyloP100

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over