ENST00000494710.6:c.115+9892G>C

Variant names:

• chr1-65264541-G-C
• rs3828040
• ENST00000494710.6:c.115+9892G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000494710.6(DNAJC6):​c.115+9892G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,826 control chromosomes in the GnomAD database, including 15,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15431 hom., cov: 31)
• Consequence: DNAJC6 ENST00000494710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.655
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-65264541-G-C is Benign according to our data. Variant chr1-65264541-G-C is described in ClinVar as Benign. ClinVar VariationId is 1282584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000494710.6. 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_014787.4		c.-370G>C		upstream_gene	N/A	NP_055602.1	O75061-1
	DNAJC6	NM_001256865.2		c.-522G>C		upstream_gene	N/A	NP_001243794.1	O75061-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	ENST00000494710.6	TSL:5	c.115+9892G>C		intron	N/A	ENSP00000473821.1	S4R305
	DNAJC6	ENST00000463018.5	TSL:3	n.85+16238G>C		intron	N/A
	DNAJC6	ENST00000395325.7	TSL:1	c.-370G>C		upstream_gene	N/A	ENSP00000378735.3	O75061-1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68240 AN: 151708 Hom.: 15425 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.450 AC: 68283 AN: 151826 Hom.: 15431 Cov.: 31 AF XY: 0.450 AC XY: 33400 AN XY: 74168

African (AFR) AF: 0.401 AC: 16593 AN: 41368

American (AMR) AF: 0.453 AC: 6918 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2898 AN: 5144

South Asian (SAS) AF: 0.527 AC: 2533 AN: 4804

European-Finnish (FIN) AF: 0.414 AC: 4371 AN: 10554

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32086 AN: 67924

Other (OTH) AF: 0.471 AC: 992 AN: 2106

Alfa AF: 0.445 Hom.: 1940

Bravo AF: 0.450

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.65
PhyloP100		0.66
PromoterAI		-0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3828040; hg19: chr1-65730224; COSMIC: COSV54780849;