dbSNP rs10493377: DNAJC6:c.*544A>G (chr1-65413569-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001256864.2(DNAJC6):c.*544A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,946 control chromosomes in the GnomAD database, including 18,498 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 18488 hom., cov: 31)

Exomes 𝑓: 0.46 ( 10 hom. )

Consequence

DNAJC6
NM_001256864.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.211

Publications

31 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2 link	c.*544A>G	3_prime_UTR_variant	Exon 19 of 19	ENST00000371069.5	NP_001243793.1	O75061-2
DNAJC6	NM_014787.4 link	c.*544A>G	3_prime_UTR_variant	Exon 19 of 19		NP_055602.1	O75061-1
DNAJC6	NM_001256865.2 link	c.*544A>G	3_prime_UTR_variant	Exon 20 of 20		NP_001243794.1	O75061-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAJC6	ENST00000371069.5 link	c.*544A>G	3_prime_UTR_variant	Exon 19 of 19	1	NM_001256864.2	ENSP00000360108.4	O75061-2
DNAJC6	ENST00000395325.7 link	c.*544A>G	3_prime_UTR_variant	Exon 19 of 19	1		ENSP00000378735.3	O75061-1
DNAJC6	ENST00000263441.11 link	c.*544A>G	3_prime_UTR_variant	Exon 20 of 20	2		ENSP00000263441.7	O75061-4

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73873

AN:

151716

Hom.:

18460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.573

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.487

GnomAD4 exome

AF:

0.465

AC:

AN:

114

Hom.:

Cov.:

AF XY:

0.481

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.667

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.453

AC:

AN:

106

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.487

AC:

73949

AN:

151832

Hom.:

18488

Cov.:

AF XY:

0.491

AC XY:

36446

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.505

AC:

20908

AN:

41396

American (AMR)

AF:

0.469

AC:

7150

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1544

AN:

3466

East Asian (EAS)

AF:

0.859

AC:

4429

AN:

5156

South Asian (SAS)

AF:

0.574

AC:

2766

AN:

4816

European-Finnish (FIN)

AF:

0.465

AC:

4897

AN:

10524

Middle Eastern (MID)

AF:

0.500

AC:

145

AN:

290

European-Non Finnish (NFE)

AF:

0.451

AC:

30661

AN:

67914

Other (OTH)

AF:

0.487

AC:

1024

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1901

3802

5702

7603

9504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.463

Hom.:

30898

Bravo

AF:

0.486

Asia WGS

AF:

0.645

AC:

2245

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.68

(source)

DANN

Benign

0.51

PhyloP100

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Computational scores

Splicing

Publications

Other links and lift over