1-65265168-C-T

Variant names:

• chr1-65265168-C-T
• rs1749970
• ENST00000395325.7:c.22+236C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014787.4(DNAJC6):​c.22+236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 151,932 control chromosomes in the GnomAD database, including 35,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (35917 hom., cov: 32)
• Consequence: DNAJC6 NM_014787.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.235
• Publications: 1 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-65265168-C-T is Benign according to our data. Variant chr1-65265168-C-T is described in ClinVar as Benign. ClinVar VariationId is 1280775.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014787.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	NM_014787.4		c.22+236C>T		intron	N/A	NP_055602.1	O75061-1
	DNAJC6	NM_001256865.2		c.-131+236C>T		intron	N/A	NP_001243794.1	O75061-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	ENST00000395325.7	TSL:1	c.22+236C>T		intron	N/A	ENSP00000378735.3	O75061-1
	DNAJC6	ENST00000263441.11	TSL:2	c.-131+236C>T		intron	N/A	ENSP00000263441.7	O75061-4
	DNAJC6	ENST00000494710.6	TSL:5	c.115+10519C>T		intron	N/A	ENSP00000473821.1	S4R305

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103357 AN: 151816 Hom.: 35903 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.681 AC: 103417 AN: 151932 Hom.: 35917 Cov.: 32 AF XY: 0.679 AC XY: 50457 AN XY: 74272

African (AFR) AF: 0.532 AC: 21992 AN: 41338

American (AMR) AF: 0.671 AC: 10249 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2763 AN: 3464

East Asian (EAS) AF: 0.771 AC: 4000 AN: 5186

South Asian (SAS) AF: 0.874 AC: 4212 AN: 4820

European-Finnish (FIN) AF: 0.640 AC: 6752 AN: 10552

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51152 AN: 67984

Other (OTH) AF: 0.693 AC: 1464 AN: 2112

Alfa AF: 0.699 Hom.: 4861

Bravo AF: 0.673

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		-0.23
PromoterAI		0.0084	Neutral
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: rs1749970; hg19: chr1-65730851;