1-65309947-G-T

Variant names:

• chr1-65309947-G-T
• rs906548572
• NM_001256864.2:c.193+9G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001256864.2(DNAJC6):​c.193+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,441,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.01
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-65309947-G-T is Benign according to our data. Variant chr1-65309947-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3705421.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	NM_001256864.2	MANE Select	c.193+9G>T		intron	N/A	NP_001243793.1	O75061-2
	DNAJC6	NM_014787.4		c.22+45015G>T		intron	N/A	NP_055602.1	O75061-1
	DNAJC6	NM_001256865.2		c.-130-35664G>T		intron	N/A	NP_001243794.1	O75061-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC6	ENST00000371069.5	TSL:1 MANE Select	c.193+9G>T		intron	N/A	ENSP00000360108.4	O75061-2
	DNAJC6	ENST00000395325.7	TSL:1	c.22+45015G>T		intron	N/A	ENSP00000378735.3	O75061-1
	DNAJC6	ENST00000263441.11	TSL:2	c.-130-35664G>T		intron	N/A	ENSP00000263441.7	O75061-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000225 AC: 1 AN: 44440 AF XY: 0.0000426

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000233 AC: 3 AN: 1289030 Hom.: 0 Cov.: 34 AF XY: 0.00000159 AC XY: 1 AN XY: 628684

African (AFR) AF: 0.00 AC: 0 AN: 25352

American (AMR) AF: 0.000144 AC: 3 AN: 20864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19088

East Asian (EAS) AF: 0.00 AC: 0 AN: 29334

South Asian (SAS) AF: 0.00 AC: 0 AN: 63910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4150

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029486

Other (OTH) AF: 0.00 AC: 0 AN: 52830

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Juvenile onset Parkinson disease 19A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		2.0
PromoterAI		-0.0015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs906548572; hg19: chr1-65775630;