dbSNP rs753576283: DNAJC6:c.194-5G>A (chr1-65364630-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001256864.2(DNAJC6):c.194-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,099,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

DNAJC6
NM_001256864.2 splice_region, intron

Scores

Splicing: ADA: 0.08598

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2 link	c.194-5G>A	splice_region_variant, intron_variant	Intron 1 of 18	ENST00000371069.5	NP_001243793.1	O75061-2
DNAJC6	NM_014787.4 link	c.23-5G>A	splice_region_variant, intron_variant	Intron 1 of 18		NP_055602.1	O75061-1
DNAJC6	NM_001256865.2 link	c.-17-5G>A	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>A		splice_region_variant, intron_variant	Intron 1 of 18	1	NM_001256864.2	ENSP00000360108.4		O75061-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

95330

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1099050

Hom.:

Cov.:

AF XY:

0.00000374

AC XY:

AN XY:

535056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23436

American (AMR)

AF:

0.00

AC:

AN:

13970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16112

East Asian (EAS)

AF:

0.00

AC:

AN:

23608

South Asian (SAS)

AF:

0.0000264

AC:

AN:

37930

European-Finnish (FIN)

AF:

0.0000325

AC:

AN:

30724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3330

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

905542

Other (OTH)

AF:

0.00

AC:

AN:

44398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.090

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.086

dbscSNV1_RF

Benign

0.52

SpliceAI score (max)

0.98

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.98

Position offset: 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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over