chr1-65413569-A-G

Variant names:

• chr1-65413569-A-G
• rs10493377
• NM_001256864.2:c.*544A>G

Variant summary

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

The NM_001256864.2(DNAJC6):​c.*544A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,946 control chromosomes in the GnomAD database, including 18,498 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 0.49 (18488 hom., cov: 31)
  • Exomes 𝑓: 0.46 (10 hom.)
• Consequence: DNAJC6 NM_001256864.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 31 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.*544A>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.*544A>G		3_prime_UTR_variant	Exon 19 of 19		NP_055602.1
DNAJC6	NM_001256865.2	c.*544A>G		3_prime_UTR_variant	Exon 20 of 20		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.*544A>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_001256864.2	ENSP00000360108.4
DNAJC6	ENST00000395325.7	c.*544A>G		3_prime_UTR_variant	Exon 19 of 19	1		ENSP00000378735.3
DNAJC6	ENST00000263441.11	c.*544A>G		3_prime_UTR_variant	Exon 20 of 20	2		ENSP00000263441.7

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73873 AN: 151716 Hom.: 18460 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.465 AC: 53 AN: 114 Hom.: 10 Cov.: 0 AF XY: 0.481 AC XY: 26 AN XY: 54

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.667 AC: 4 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.453 AC: 48 AN: 106

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.487 AC: 73949 AN: 151832 Hom.: 18488 Cov.: 31 AF XY: 0.491 AC XY: 36446 AN XY: 74198

African (AFR) AF: 0.505 AC: 20908 AN: 41396

American (AMR) AF: 0.469 AC: 7150 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3466

East Asian (EAS) AF: 0.859 AC: 4429 AN: 5156

South Asian (SAS) AF: 0.574 AC: 2766 AN: 4816

European-Finnish (FIN) AF: 0.465 AC: 4897 AN: 10524

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.451 AC: 30661 AN: 67914

Other (OTH) AF: 0.487 AC: 1024 AN: 2102

Alfa AF: 0.463 Hom.: 30898

Bravo AF: 0.486

Asia WGS AF: 0.645 AC: 2245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.51
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs10493377; hg19: chr1-65879252;