Variant rs187965193 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001256864.2(DNAJC6):c.996-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000948 in 1,611,568 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 12 hom. )

Consequence

DNAJC6
NM_001256864.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0005125

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.764

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 1-65386803-T-C is Benign according to our data. Variant chr1-65386803-T-C is described in ClinVar as [Benign]. Clinvar id is 541545.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DNAJC6	NM_001256864.2 linkuse as main transcript	c.996-9T>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_001256865.2 linkuse as main transcript	c.786-9T>C	splice_polypyrimidine_tract_variant, intron_variant		NP_001243794.1
DNAJC6	NM_014787.4 linkuse as main transcript	c.825-9T>C	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.996-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001256864.2	ENSP00000360108	P4	O75061-2

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0211

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00212

AC:

531

AN:

250984

Hom.:

AF XY:

0.00205

AC XY:

278

AN XY:

135640

show subpopulations

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 SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0214

Gnomad NFE exome

AF:

0.000476

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.000872

AC:

1273

AN:

1459236

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

617

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0000892

Gnomad4 OTH exome

AF:

0.000829

GnomAD4 genome

AF:

0.00167

AC:

255

AN:

152332

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0211

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.0000945

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Juvenile onset Parkinson disease 19A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00051

dbscSNV1_RF

Benign

0.014

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