rs4592284

Variant names:

• chr1-65401708-C-G
• rs4592284
• NM_001256864.2:c.2108-53C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-65401708-C-G
• chr1-65401708-C-A
• chr1-65401708-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256864.2(DNAJC6):​c.2108-53C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,574,990 control chromosomes in the GnomAD database, including 288,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34865 hom., cov: 31)
  • Exomes 𝑓: 0.59 (253794 hom.)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0920
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-65401708-C-G is Benign according to our data. Variant chr1-65401708-C-G is described in ClinVar as Benign. ClinVar VariationId is 1280630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	NM_001256864.2	MANE Select	c.2108-53C>G		intron	N/A	NP_001243793.1	O75061-2
	DNAJC6	NM_014787.4		c.1937-53C>G		intron	N/A	NP_055602.1	O75061-1
	DNAJC6	NM_001256865.2		c.1898-53C>G		intron	N/A	NP_001243794.1	O75061-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	ENST00000371069.5	TSL:1 MANE Select	c.2108-53C>G		intron	N/A	ENSP00000360108.4	O75061-2
	DNAJC6	ENST00000395325.7	TSL:1	c.1937-53C>G		intron	N/A	ENSP00000378735.3	O75061-1
	DNAJC6	ENST00000263441.11	TSL:2	c.1898-53C>G		intron	N/A	ENSP00000263441.7	O75061-4

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101312 AN: 151912 Hom.: 34828 Cov.: 31

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.656

GnomAD4 exome AF: 0.593 AC: 843833 AN: 1422960 Hom.: 253794 AF XY: 0.596 AC XY: 420996 AN XY: 706492

African (AFR) AF: 0.864 AC: 26742 AN: 30940

American (AMR) AF: 0.627 AC: 21075 AN: 33604

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 15643 AN: 24124

East Asian (EAS) AF: 0.812 AC: 31766 AN: 39138

South Asian (SAS) AF: 0.689 AC: 56222 AN: 81560

European-Finnish (FIN) AF: 0.580 AC: 30384 AN: 52374

Middle Eastern (MID) AF: 0.656 AC: 3657 AN: 5572

European-Non Finnish (NFE) AF: 0.567 AC: 622531 AN: 1097046

Other (OTH) AF: 0.611 AC: 35813 AN: 58602

GnomAD4 genome AF: 0.667 AC: 101408 AN: 152030 Hom.: 34865 Cov.: 31 AF XY: 0.669 AC XY: 49670 AN XY: 74300

African (AFR) AF: 0.852 AC: 35365 AN: 41488

American (AMR) AF: 0.634 AC: 9687 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3468

East Asian (EAS) AF: 0.785 AC: 4064 AN: 5174

South Asian (SAS) AF: 0.697 AC: 3356 AN: 4818

European-Finnish (FIN) AF: 0.568 AC: 5998 AN: 10562

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38567 AN: 67930

Other (OTH) AF: 0.660 AC: 1392 AN: 2108

Alfa AF: 0.619 Hom.: 3749

Bravo AF: 0.678

Asia WGS AF: 0.742 AC: 2579 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		-0.092
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4592284; hg19: chr1-65867391;