Genetic Variant NM_001256864.2:c.193+7610G>T (chr1-65317548-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001256864.2(DNAJC6):c.193+7610G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,202 control chromosomes in the GnomAD database, including 1,464 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 0.12 ( 1464 hom., cov: 33)

Consequence

DNAJC6
NM_001256864.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.200

Publications

5 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, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp
atypical juvenile parkinsonism
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNAJC6 links:

ENSG00000290094 (HGNC:):

ENSG00000290094 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001256864.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
DNAJC6	NM_001256864.2	MANE Select	c.193+7610G>T	intron	N/A	NP_001243793.1	O75061-2
DNAJC6	NM_014787.4		c.23-47087G>T	intron	N/A	NP_055602.1	O75061-1
DNAJC6	NM_001256865.2		c.-130-28063G>T	intron	N/A	NP_001243794.1	O75061-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJC6	ENST00000371069.5	TSL:1 MANE Select	c.193+7610G>T	intron	N/A	ENSP00000360108.4	O75061-2
DNAJC6	ENST00000395325.7	TSL:1	c.23-47087G>T	intron	N/A	ENSP00000378735.3	O75061-1
DNAJC6	ENST00000263441.11	TSL:2	c.-130-28063G>T	intron	N/A	ENSP00000263441.7	O75061-4

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18276

AN:

152084

Hom.:

1453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.0319

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0527

Gnomad OTH

AF:

0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.120

AC:

18334

AN:

152202

Hom.:

1464

Cov.:

AF XY:

0.129

AC XY:

9601

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.189

AC:

7863

AN:

41518

American (AMR)

AF:

0.145

AC:

2212

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

362

AN:

3472

East Asian (EAS)

AF:

0.268

AC:

1385

AN:

5168

South Asian (SAS)

AF:

0.237

AC:

1141

AN:

4824

European-Finnish (FIN)

AF:

0.139

AC:

1476

AN:

10596

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0527

AC:

3583

AN:

68018

Other (OTH)

AF:

0.120

AC:

253

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

803

1606

2408

3211

4014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.0741

Hom.:

2709

Bravo

AF:

0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.45

PhyloP100

0.20

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over