1-65364630-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001256864.2(DNAJC6):c.194-5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAJC6
NM_001256864.2 splice_region, intron

Scores

Splicing: ADA: 0.00002371

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0900

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-65364630-G-T is Benign according to our data. Variant chr1-65364630-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 474676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2 link	c.194-5G>T	splice_region_variant, intron_variant	Intron 1 of 18	ENST00000371069.5	NP_001243793.1	O75061-2
DNAJC6	NM_014787.4 link	c.23-5G>T	splice_region_variant, intron_variant	Intron 1 of 18		NP_055602.1	O75061-1
DNAJC6	NM_001256865.2 link	c.-17-5G>T	splice_region_variant, intron_variant	Intron 2 of 19		NP_001243794.1	O75061-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5 link	c.194-5G>T		splice_region_variant, intron_variant	Intron 1 of 18	1	NM_001256864.2	ENSP00000360108.4		O75061-2

Frequencies

GnomAD3 genomes

AF:

0.00315

AC:

314

AN:

99622

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00112

Gnomad AMI

AF:

0.00489

Gnomad AMR

AF:

0.00586

Gnomad ASJ

AF:

0.00200

Gnomad EAS

AF:

0.0131

Gnomad SAS

AF:

0.000982

Gnomad FIN

AF:

0.00865

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00217

GnomAD2 exomes

AF:

0.00359

AC:

342

AN:

95330

AF XY:

0.00349

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.00622

Gnomad EAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.00127

Gnomad NFE exome

AF:

0.00216

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00289

AC:

3167

AN:

1094870

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

1805

AN XY:

532844

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00120

AC:

AN:

23378

American (AMR)

AF:

0.0196

AC:

270

AN:

13748

Ashkenazi Jewish (ASJ)

AF:

0.00625

AC:

100

AN:

16010

East Asian (EAS)

AF:

0.00903

AC:

210

AN:

23258

South Asian (SAS)

AF:

0.0135

AC:

504

AN:

37382

European-Finnish (FIN)

AF:

0.00465

AC:

142

AN:

30570

Middle Eastern (MID)

AF:

0.00181

AC:

AN:

3320

European-Non Finnish (NFE)

AF:

0.00194

AC:

1754

AN:

903002

Other (OTH)

AF:

0.00346

AC:

153

AN:

44202

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.294

Heterozygous variant carriers

226

453

679

906

1132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00315

AC:

314

AN:

99662

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

178

AN XY:

47590

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00112

AC:

AN:

26788

American (AMR)

AF:

0.00586

AC:

AN:

9046

Ashkenazi Jewish (ASJ)

AF:

0.00200

AC:

AN:

2504

East Asian (EAS)

AF:

0.0131

AC:

AN:

2670

South Asian (SAS)

AF:

0.000986

AC:

AN:

3042

European-Finnish (FIN)

AF:

0.00865

AC:

AN:

5200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.00284

AC:

137

AN:

48204

Other (OTH)

AF:

0.00216

AC:

AN:

1390

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.265

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0130

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Juvenile onset Parkinson disease 19A

Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 25, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.8

(source)

DANN

Benign

0.73

PhyloP100

0.090

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0020

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-65364630-G-T

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