rs6588131

Variant names:

• chr1-65335879-C-A
• rs6588131
• NM_001256864.2:c.193+25941C>A

Variant summary

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

The NM_001256864.2(DNAJC6):​c.193+25941C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,858 control chromosomes in the GnomAD database, including 22,042 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 0.53 (22042 hom., cov: 31)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• 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

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 (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.193+25941C>A		intron_variant	Intron 1 of 18	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.23-28756C>A		intron_variant	Intron 1 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.-130-9732C>A		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.193+25941C>A		intron_variant	Intron 1 of 18	1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80918 AN: 151740 Hom.: 22034 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.533 AC: 80962 AN: 151858 Hom.: 22042 Cov.: 31 AF XY: 0.521 AC XY: 38671 AN XY: 74208

African (AFR) AF: 0.606 AC: 25097 AN: 41392

American (AMR) AF: 0.440 AC: 6720 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1778 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1678 AN: 5152

South Asian (SAS) AF: 0.403 AC: 1929 AN: 4790

European-Finnish (FIN) AF: 0.409 AC: 4310 AN: 10544

Middle Eastern (MID) AF: 0.493 AC: 143 AN: 290

European-Non Finnish (NFE) AF: 0.555 AC: 37690 AN: 67936

Other (OTH) AF: 0.540 AC: 1139 AN: 2108

Alfa AF: 0.529 Hom.: 4098

Bravo AF: 0.540

Asia WGS AF: 0.365 AC: 1270 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.80
PhyloP100		-0.33
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: rs6588131; hg19: chr1-65801562;