1-65389615-C-T

Position:

chr1-65389615-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000371069.5(DNAJC6):c.1456C>T(p.Leu486Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00204 in 1,614,060 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

DNAJC6
ENST00000371069.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070246756).

BP6

Variant 1-65389615-C-T is Benign according to our data. Variant chr1-65389615-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-65389615-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1637/152280) while in subpopulation AFR AF= 0.0381 (1581/41536). AF 95% confidence interval is 0.0365. There are 22 homozygotes in gnomad4. There are 754 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAJC6	NM_001256864.2 linkuse as main transcript	c.1456C>T	p.Leu486Phe	missense_variant	11/19	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4 linkuse as main transcript	c.1285C>T	p.Leu429Phe	missense_variant	11/19		NP_055602.1
DNAJC6	NM_001256865.2 linkuse as main transcript	c.1246C>T	p.Leu416Phe	missense_variant	12/20		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5 linkuse as main transcript	c.1456C>T	p.Leu486Phe	missense_variant	11/19	1	NM_001256864.2	ENSP00000360108	P4	O75061-2
DNAJC6	ENST00000395325.7 linkuse as main transcript	c.1285C>T	p.Leu429Phe	missense_variant	11/19	1		ENSP00000378735	A1	O75061-1
DNAJC6	ENST00000263441.11 linkuse as main transcript	c.1246C>T	p.Leu416Phe	missense_variant	12/20	2		ENSP00000263441	A1	O75061-4
DNAJC6	ENST00000494710.6 linkuse as main transcript	c.1378C>T	p.Leu460Phe	missense_variant	11/12	5		ENSP00000473821

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1635

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00276

AC:

693

AN:

251382

Hom.:

AF XY:

0.00208

AC XY:

283

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0390

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00113

AC:

1651

AN:

1461780

Hom.:

Cov.:

AF XY:

0.000938

AC XY:

682

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0416

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.0107

AC:

1637

AN:

152280

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

754

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0381

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.0122

ESP6500AA

AF:

0.0315

AC:

139

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00357

AC:

433

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Juvenile onset Parkinson disease 19A

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 24, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 13, 2023	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 28, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 27, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

.;.;T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.94

D;D;D;D

MetaRNN

Benign

0.0070

T;T;T;T

MetaSVM

Uncertain

0.54

MutationAssessor

Uncertain

2.7

.;.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.7

.;D;D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.012

.;D;D;D

Sift4G

Uncertain

0.013

D;T;T;T

Polyphen

0.97, 1.0

.;.;D;D

Vest4

0.37, 0.35

MVP

0.66

MPC

0.35

ClinPred

0.024

GERP RS

4.6

Varity_R

0.19

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

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