NM_001256864.2:c.194-14659C>T

Variant names:

• chr1-65349976-C-T
• rs1413885
• NM_001256864.2:c.194-14659C>T

Variant summary

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

The NM_001256864.2(DNAJC6):​c.194-14659C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,052 control chromosomes in the GnomAD database, including 41,277 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 0.72 (41277 hom., cov: 32)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.194-14659C>T		intron_variant	Intron 1 of 18	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.23-14659C>T		intron_variant	Intron 1 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.-18+4253C>T		intron_variant	Intron 2 of 19		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.194-14659C>T		intron_variant	Intron 1 of 18	1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109980 AN: 151934 Hom.: 41211 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.724 AC: 110105 AN: 152052 Hom.: 41277 Cov.: 32 AF XY: 0.725 AC XY: 53834 AN XY: 74282

African (AFR) AF: 0.928 AC: 38537 AN: 41530

American (AMR) AF: 0.749 AC: 11431 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2319 AN: 3466

East Asian (EAS) AF: 0.828 AC: 4285 AN: 5178

South Asian (SAS) AF: 0.712 AC: 3434 AN: 4822

European-Finnish (FIN) AF: 0.601 AC: 6329 AN: 10538

Middle Eastern (MID) AF: 0.703 AC: 204 AN: 290

European-Non Finnish (NFE) AF: 0.610 AC: 41427 AN: 67940

Other (OTH) AF: 0.745 AC: 1571 AN: 2110

Alfa AF: 0.659 Hom.: 75490

Bravo AF: 0.745

Asia WGS AF: 0.773 AC: 2689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.38
PhyloP100		-0.77
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: rs1413885; hg19: chr1-65815659;