Genetic Variant NM_001256864.2:c.193+9G>A (chr1-65309947-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001256864.2(DNAJC6):c.193+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,289,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

DNAJC6
NM_001256864.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

0 publications found

Variant links:

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

DNAJC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=-0.69).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000155

AC:

AN:

1289030

Hom.:

Cov.:

AF XY:

0.00000318

AC XY:

AN XY:

628684

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25352

American (AMR)

AF:

0.00

AC:

AN:

20864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19088

East Asian (EAS)

AF:

0.00

AC:

AN:

29334

South Asian (SAS)

AF:

0.00

AC:

AN:

63910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4150

European-Non Finnish (NFE)

AF:

0.00000194

AC:

AN:

1029486

Other (OTH)

AF:

0.00

AC:

AN:

52830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

2.0

PromoterAI

0.027

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over