Genetic Variant NM_001256864.2:c.186C>T (chr1-65309931-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001256864.2(DNAJC6):c.186C>T(p.Asp62Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000254 in 1,496,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

DNAJC6
NM_001256864.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.57

Publications

0 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 1-65309931-C-T is Benign according to our data. Variant chr1-65309931-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 705033.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256864.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC6	NM_001256864.2	MANE Select	c.186C>T	p.Asp62Asp	synonymous	Exon 1 of 19	NP_001243793.1	O75061-2
DNAJC6	NM_014787.4		c.22+44999C>T		intron	N/A	NP_055602.1	O75061-1
DNAJC6	NM_001256865.2		c.-130-35680C>T		intron	N/A	NP_001243794.1	O75061-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJC6	ENST00000371069.5	TSL:1 MANE Select	c.186C>T	p.Asp62Asp	synonymous	Exon 1 of 19	ENSP00000360108.4	O75061-2
DNAJC6	ENST00000395325.7	TSL:1	c.22+44999C>T		intron	N/A	ENSP00000378735.3	O75061-1
DNAJC6	ENST00000263441.11	TSL:2	c.-130-35680C>T		intron	N/A	ENSP00000263441.7	O75061-4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.0000212

AC:

AN:

94362

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000395

GnomAD4 exome

AF:

0.0000238

AC:

AN:

1343850

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

660130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27642

American (AMR)

AF:

0.0000340

AC:

AN:

29410

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21880

East Asian (EAS)

AF:

0.000189

AC:

AN:

31674

South Asian (SAS)

AF:

0.00

AC:

AN:

72770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4826

European-Non Finnish (NFE)

AF:

0.00000379

AC:

AN:

1054080

Other (OTH)

AF:

0.000379

AC:

AN:

55346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

AF:

0.0000394

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000581

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.000957

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Juvenile onset Parkinson disease 19A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

4.6

PromoterAI

0.095

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=83/17

polymorphism

(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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over