1-65341729-T-C

Variant names:

• chr1-65341729-T-C
• rs12086738
• NM_001256864.2:c.194-22906T>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.194-22906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,778 control chromosomes in the GnomAD database, including 31,343 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 0.63 (31343 hom., cov: 29)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.194-22906T>C		intron_variant	Intron 1 of 18	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.23-22906T>C		intron_variant	Intron 1 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.-130-3882T>C		intron_variant	Intron 1 of 19		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.194-22906T>C		intron_variant	Intron 1 of 18	1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95086 AN: 151660 Hom.: 31298 Cov.: 29

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.627 AC: 95175 AN: 151778 Hom.: 31343 Cov.: 29 AF XY: 0.616 AC XY: 45648 AN XY: 74154

African (AFR) AF: 0.836 AC: 34593 AN: 41396

American (AMR) AF: 0.501 AC: 7627 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2095 AN: 3472

East Asian (EAS) AF: 0.423 AC: 2172 AN: 5134

South Asian (SAS) AF: 0.556 AC: 2669 AN: 4798

European-Finnish (FIN) AF: 0.425 AC: 4467 AN: 10516

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39463 AN: 67924

Other (OTH) AF: 0.630 AC: 1327 AN: 2108

Alfa AF: 0.589 Hom.: 40388

Bravo AF: 0.639

Asia WGS AF: 0.495 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		-0.038
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: rs12086738; hg19: chr1-65807412;