1-65384204-G-A

Variant names:

• chr1-65384204-G-A
• rs61753391
• NM_001256864.2:c.678G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001256864.2(DNAJC6):​c.678G>A​(p.Ala226Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,516,340 control chromosomes in the GnomAD database, including 483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (30 hom., cov: 32)
  • Exomes 𝑓: 0.024 (453 hom.)
• Consequence: DNAJC6 NM_001256864.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.199
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-65384204-G-A is Benign according to our data. Variant chr1-65384204-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.199 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.018 (2733/152158) while in subpopulation NFE AF = 0.027 (1837/67996). AF 95% confidence interval is 0.026. There are 30 homozygotes in GnomAd4. There are 1314 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256864.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	NM_001256864.2	MANE Select	c.678G>A	p.Ala226Ala	synonymous	Exon 6 of 19	NP_001243793.1
	DNAJC6	NM_014787.4		c.507G>A	p.Ala169Ala	synonymous	Exon 6 of 19	NP_055602.1
	DNAJC6	NM_001256865.2		c.468G>A	p.Ala156Ala	synonymous	Exon 7 of 20	NP_001243794.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	ENST00000371069.5	TSL:1 MANE Select	c.678G>A	p.Ala226Ala	synonymous	Exon 6 of 19	ENSP00000360108.4
	DNAJC6	ENST00000395325.7	TSL:1	c.507G>A	p.Ala169Ala	synonymous	Exon 6 of 19	ENSP00000378735.3
	DNAJC6	ENST00000263441.11	TSL:2	c.468G>A	p.Ala156Ala	synonymous	Exon 7 of 20	ENSP00000263441.7

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2736 AN: 152040 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00444

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00499

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.0203 AC: 3818 AN: 188090 AF XY: 0.0206

Gnomad AFR exome AF: 0.00424

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0220

Gnomad NFE exome AF: 0.0294

Gnomad OTH exome AF: 0.0299

GnomAD4 exome AF: 0.0236 AC: 32240 AN: 1364182 Hom.: 453 Cov.: 30 AF XY: 0.0231 AC XY: 15589 AN XY: 675412

African (AFR) AF: 0.00454 AC: 131 AN: 28824

American (AMR) AF: 0.0137 AC: 410 AN: 29924

Ashkenazi Jewish (ASJ) AF: 0.0183 AC: 423 AN: 23168

East Asian (EAS) AF: 0.0000299 AC: 1 AN: 33450

South Asian (SAS) AF: 0.00670 AC: 469 AN: 69982

European-Finnish (FIN) AF: 0.0235 AC: 1215 AN: 51612

Middle Eastern (MID) AF: 0.0398 AC: 217 AN: 5450

European-Non Finnish (NFE) AF: 0.0263 AC: 28072 AN: 1065668

Other (OTH) AF: 0.0232 AC: 1302 AN: 56104

GnomAD4 genome AF: 0.0180 AC: 2733 AN: 152158 Hom.: 30 Cov.: 32 AF XY: 0.0177 AC XY: 1314 AN XY: 74386

African (AFR) AF: 0.00446 AC: 185 AN: 41526

American (AMR) AF: 0.0190 AC: 290 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.00457 AC: 22 AN: 4810

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10598

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1837 AN: 67996

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0233 Hom.: 102

Bravo AF: 0.0174

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Oct 06, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Juvenile onset Parkinson disease 19A Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.8
DANN	Benign	0.72
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs61753391; hg19: chr1-65849887; COSMIC: COSV104554443; COSMIC: COSV104554443;