rs1570868

Variant names:

• chr1-65364925-T-C
• rs1570868
• NM_001256864.2:c.344+140T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256864.2(DNAJC6):​c.344+140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,207,840 control chromosomes in the GnomAD database, including 188,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21711 hom., cov: 31)
  • Exomes 𝑓: 0.56 (166519 hom.)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.72
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-65364925-T-C is Benign according to our data. Variant chr1-65364925-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.344+140T>C		intron_variant	Intron 2 of 18	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.173+140T>C		intron_variant	Intron 2 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.134+140T>C		intron_variant	Intron 3 of 19		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.344+140T>C		intron_variant	Intron 2 of 18	1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80570 AN: 151796 Hom.: 21709 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.556 AC: 587056 AN: 1055926 Hom.: 166519 AF XY: 0.559 AC XY: 296221 AN XY: 529750

African (AFR) AF: 0.477 AC: 11523 AN: 24144

American (AMR) AF: 0.475 AC: 14140 AN: 29750

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 10508 AN: 18192

East Asian (EAS) AF: 0.290 AC: 10762 AN: 37052

South Asian (SAS) AF: 0.598 AC: 36423 AN: 60926

European-Finnish (FIN) AF: 0.471 AC: 17018 AN: 36152

Middle Eastern (MID) AF: 0.626 AC: 2932 AN: 4682

European-Non Finnish (NFE) AF: 0.574 AC: 458271 AN: 798730

Other (OTH) AF: 0.550 AC: 25479 AN: 46298

GnomAD4 genome AF: 0.531 AC: 80613 AN: 151914 Hom.: 21711 Cov.: 31 AF XY: 0.525 AC XY: 38942 AN XY: 74198

African (AFR) AF: 0.487 AC: 20199 AN: 41444

American (AMR) AF: 0.533 AC: 8118 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1529 AN: 5152

South Asian (SAS) AF: 0.595 AC: 2864 AN: 4810

European-Finnish (FIN) AF: 0.445 AC: 4694 AN: 10540

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39282 AN: 67936

Other (OTH) AF: 0.560 AC: 1183 AN: 2114

Alfa AF: 0.568 Hom.: 45832

Bravo AF: 0.529

Asia WGS AF: 0.431 AC: 1497 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.049
DANN	Benign	0.54
PhyloP100		-2.7
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: rs1570868; hg19: chr1-65830608; COSMIC: COSV54771795; COSMIC: COSV54771795;