rs3790436

Variant names:

• chr1-65410168-G-C
• rs3790436
• NM_001256864.2:c.2635-1082G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256864.2(DNAJC6):​c.2635-1082G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,958 control chromosomes in the GnomAD database, including 18,182 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 0.48 (18182 hom., cov: 32)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 5 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: 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.2635-1082G>C		intron_variant	Intron 17 of 18	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.2464-1082G>C		intron_variant	Intron 17 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.2425-1082G>C		intron_variant	Intron 18 of 19		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.2635-1082G>C		intron_variant	Intron 17 of 18	1	NM_001256864.2	ENSP00000360108.4
DNAJC6	ENST00000395325.7	c.2464-1082G>C		intron_variant	Intron 17 of 18	1		ENSP00000378735.3
DNAJC6	ENST00000263441.11	c.2425-1082G>C		intron_variant	Intron 18 of 19	2		ENSP00000263441.7

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73437 AN: 151840 Hom.: 18168 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.484 AC: 73474 AN: 151958 Hom.: 18182 Cov.: 32 AF XY: 0.484 AC XY: 35912 AN XY: 74258

African (AFR) AF: 0.556 AC: 23025 AN: 41428

American (AMR) AF: 0.451 AC: 6889 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1514 AN: 3466

East Asian (EAS) AF: 0.748 AC: 3869 AN: 5172

South Asian (SAS) AF: 0.486 AC: 2343 AN: 4824

European-Finnish (FIN) AF: 0.433 AC: 4557 AN: 10532

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29902 AN: 67940

Other (OTH) AF: 0.467 AC: 988 AN: 2114

Alfa AF: 0.455 Hom.: 2168

Bravo AF: 0.490

Asia WGS AF: 0.572 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.63
PhyloP100		1.8
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: rs3790436; hg19: chr1-65875851;