1-65378971-T-G

Variant names:

• chr1-65378971-T-G
• rs10493375
• NM_001256864.2:c.544-431T>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.544-431T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,148 control chromosomes in the GnomAD database, including 8,268 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 0.25 (8268 hom., cov: 33)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

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.544-431T>G		intron	N/A	NP_001243793.1
	DNAJC6	NM_014787.4		c.373-431T>G		intron	N/A	NP_055602.1
	DNAJC6	NM_001256865.2		c.334-431T>G		intron	N/A	NP_001243794.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	ENST00000371069.5	TSL:1 MANE Select	c.544-431T>G		intron	N/A	ENSP00000360108.4
	DNAJC6	ENST00000395325.7	TSL:1	c.373-431T>G		intron	N/A	ENSP00000378735.3
	DNAJC6	ENST00000263441.11	TSL:2	c.334-431T>G		intron	N/A	ENSP00000263441.7

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37886 AN: 152030 Hom.: 8247 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.250 AC: 37966 AN: 152148 Hom.: 8268 Cov.: 33 AF XY: 0.256 AC XY: 19050 AN XY: 74394

African (AFR) AF: 0.551 AC: 22831 AN: 41466

American (AMR) AF: 0.216 AC: 3296 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3148 AN: 5162

South Asian (SAS) AF: 0.304 AC: 1467 AN: 4828

European-Finnish (FIN) AF: 0.159 AC: 1687 AN: 10606

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0646 AC: 4394 AN: 68020

Other (OTH) AF: 0.221 AC: 466 AN: 2108

Alfa AF: 0.123 Hom.: 3269

Bravo AF: 0.268

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.64
PhyloP100		-0.36
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: rs10493375; hg19: chr1-65844654;