rs753576283

Variant names:

• chr1-65364630-G-A
• rs753576283
• NM_001256864.2:c.194-5G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-65364630-G-A
• chr1-65364630-G-T

Variant summary

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

The ENST00000371069.5(DNAJC6):​c.194-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,099,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: DNAJC6 ENST00000371069.5 splice_region, intron
• Scores: Splicing: ADA: 0.08598
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• 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: 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371069.5. 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.194-5G>A		splice_region intron	N/A	NP_001243793.1
	DNAJC6	NM_014787.4		c.23-5G>A		splice_region intron	N/A	NP_055602.1
	DNAJC6	NM_001256865.2		c.-17-5G>A		splice_region 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.194-5G>A		splice_region intron	N/A	ENSP00000360108.4
	DNAJC6	ENST00000395325.7	TSL:1	c.23-5G>A		splice_region intron	N/A	ENSP00000378735.3
	DNAJC6	ENST00000263441.11	TSL:2	c.-17-5G>A		splice_region intron	N/A	ENSP00000263441.7

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.00 AC: 0 AN: 95330 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000182 AC: 2 AN: 1099050 Hom.: 0 Cov.: 34 AF XY: 0.00000374 AC XY: 2 AN XY: 535056

African (AFR) AF: 0.00 AC: 0 AN: 23436

American (AMR) AF: 0.00 AC: 0 AN: 13970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16112

East Asian (EAS) AF: 0.00 AC: 0 AN: 23608

South Asian (SAS) AF: 0.0000264 AC: 1 AN: 37930

European-Finnish (FIN) AF: 0.0000325 AC: 1 AN: 30724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 905542

Other (OTH) AF: 0.00 AC: 0 AN: 44398

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	21
DANN	Benign	0.65
PhyloP100		0.090
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.086
dbscSNV1_RF	Benign	0.52
SpliceAI score (max)		0.98		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.98		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs753576283; hg19: chr1-65830313;