1-65285377-C-A

Variant names:

• chr1-65285377-C-A
• rs1325607
• ENST00000395325.7:c.22+20445C>A

Variant summary

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

The ENST00000395325.7(DNAJC6):​c.22+20445C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,058 control chromosomes in the GnomAD database, including 44,517 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 0.76 (44517 hom., cov: 32)
• Consequence: DNAJC6 ENST00000395325.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• 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: 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-AS1 (HGNC:58071):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_014787.4	c.22+20445C>A		intron_variant	Intron 1 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.-131+20445C>A		intron_variant	Intron 1 of 19		NP_001243794.1
DNAJC6-AS1	XR_007066154.1	n.894-5499G>T		intron_variant	Intron 2 of 2
DNAJC6-AS1	XR_007066155.1	n.894-7078G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000395325.7	c.22+20445C>A		intron_variant	Intron 1 of 18	1		ENSP00000378735.3
DNAJC6	ENST00000263441.11	c.-131+20445C>A		intron_variant	Intron 1 of 19	2		ENSP00000263441.7
DNAJC6	ENST00000494710.6	c.115+30728C>A		intron_variant	Intron 1 of 11	5		ENSP00000473821.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115479 AN: 151938 Hom.: 44489 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.760 AC: 115562 AN: 152058 Hom.: 44517 Cov.: 32 AF XY: 0.763 AC XY: 56686 AN XY: 74340

African (AFR) AF: 0.644 AC: 26686 AN: 41446

American (AMR) AF: 0.831 AC: 12706 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2920 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5160 AN: 5168

South Asian (SAS) AF: 0.923 AC: 4453 AN: 4822

European-Finnish (FIN) AF: 0.754 AC: 7978 AN: 10578

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53131 AN: 67976

Other (OTH) AF: 0.783 AC: 1653 AN: 2112

Alfa AF: 0.783 Hom.: 23949

Bravo AF: 0.761

Asia WGS AF: 0.932 AC: 3240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.61
DANN	Benign	0.62
PhyloP100		-0.14
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: rs1325607; hg19: chr1-65751060;