Variant 1-65364630-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001256864.2(DNAJC6):c.194-5G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAJC6
NM_001256864.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002371

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0900

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-65364630-G-T is Benign according to our data. Variant chr1-65364630-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 474676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-65364630-G-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DNAJC6	NM_001256864.2 linkuse as main transcript	c.194-5G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_001256865.2 linkuse as main transcript	c.-17-5G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001243794.1
DNAJC6	NM_014787.4 linkuse as main transcript	c.23-5G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_055602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5 linkuse as main transcript	c.194-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001256864.2	ENSP00000360108	P4	O75061-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

314

AN:

99622

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00112

Gnomad AMI

AF:

0.00489

Gnomad AMR

AF:

0.00586

Gnomad ASJ

AF:

0.00200

Gnomad EAS

AF:

0.0131

Gnomad SAS

AF:

0.000982

Gnomad FIN

AF:

0.00865

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00217

GnomAD3 exomes

AF:

0.00359

AC:

342

AN:

95330

Hom.:

AF XY:

0.00349

AC XY:

181

AN XY:

51790

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.00622

Gnomad EAS exome

AF:

0.0113

Gnomad SAS exome

AF:

0.00491

Gnomad FIN exome

AF:

0.00127

Gnomad NFE exome

AF:

0.00216

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00289

AC:

3167

AN:

1094870

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

1805

AN XY:

532844

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.0196

Gnomad4 ASJ exome

AF:

0.00625

Gnomad4 EAS exome

AF:

0.00903

Gnomad4 SAS exome

AF:

0.0135

Gnomad4 FIN exome

AF:

0.00465

Gnomad4 NFE exome

AF:

0.00194

Gnomad4 OTH exome

AF:

0.00346

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00315

AC:

314

AN:

99662

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

178

AN XY:

47590

show subpopulations

Gnomad4 AFR

AF:

0.00112

Gnomad4 AMR

AF:

0.00586

Gnomad4 ASJ

AF:

0.00200

Gnomad4 EAS

AF:

0.0131

Gnomad4 SAS

AF:

0.000986

Gnomad4 FIN

AF:

0.00865

Gnomad4 NFE

AF:

0.00284

Gnomad4 OTH

AF:

0.00216

Alfa

AF:

0.0130

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Juvenile onset Parkinson disease 19A

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 25, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.8

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0020

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over