rs78457562

Positions:

chr20-63930841-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025219.3(DNAJC5):c.322-10C>T 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 0.0725 in 1,612,042 control chromosomes in the GnomAD database, including 4,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 532 hom., cov: 33)

Exomes 𝑓: 0.072 ( 4431 hom. )

Consequence

DNAJC5
NM_025219.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001350

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.529

Variant links:

Genes affected

DNAJC5 (HGNC:16235): (DnaJ heat shock protein family (Hsp40) member C5) This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. The encoded protein plays a role in membrane trafficking and protein folding, and has been shown to have anti-neurodegenerative properties. The encoded protein is known to play a role in cystic fibrosis and Huntington's disease. A pseudogene of this gene is located on the short arm of chromosome 8. [provided by RefSeq, Nov 2010]

DNAJC5 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 (BayesDel_noAF=-0.82).

BP6

Variant 20-63930841-C-T is Benign according to our data. Variant chr20-63930841-C-T is described in ClinVar as [Benign]. Clinvar id is 137124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63930841-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC5	NM_025219.3 linkuse as main transcript	c.322-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000360864.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
DNAJC5	ENST00000360864.9 linkuse as main transcript	c.322-10C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_025219.3	P1	Q9H3Z4-1
DNAJC5	ENST00000470551.1 linkuse as main transcript	c.322-10C>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	2			Q9H3Z4-2
DNAJC5	ENST00000703637.1 linkuse as main transcript	c.322-10C>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant				Q9H3Z4-2

Frequencies

GnomAD3 genomes

AF:

0.0744

AC:

11319

AN:

152200

Hom.:

528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0680

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0472

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.0343

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0792

Gnomad OTH

AF:

0.0651

GnomAD3 exomes

AF:

0.0654

AC:

16368

AN:

250390

Hom.:

783

AF XY:

0.0641

AC XY:

8686

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.0668

Gnomad AMR exome

AF:

0.0315

Gnomad ASJ exome

AF:

0.0432

Gnomad EAS exome

AF:

0.00180

Gnomad SAS exome

AF:

0.0413

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.0731

Gnomad OTH exome

AF:

0.0673

GnomAD4 exome

AF:

0.0723

AC:

105498

AN:

1459724

Hom.:

4431

Cov.:

AF XY:

0.0714

AC XY:

51875

AN XY:

726160

show subpopulations

Gnomad4 AFR exome

AF:

0.0705

Gnomad4 AMR exome

AF:

0.0320

Gnomad4 ASJ exome

AF:

0.0445

Gnomad4 EAS exome

AF:

0.00242

Gnomad4 SAS exome

AF:

0.0408

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.0751

Gnomad4 OTH exome

AF:

0.0681

GnomAD4 genome

AF:

0.0745

AC:

11344

AN:

152318

Hom.:

532

Cov.:

AF XY:

0.0775

AC XY:

5770

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0685

Gnomad4 AMR

AF:

0.0470

Gnomad4 ASJ

AF:

0.0464

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.0340

Gnomad4 FIN

AF:

0.175

Gnomad4 NFE

AF:

0.0792

Gnomad4 OTH

AF:

0.0653

Alfa

AF:

0.0751

Hom.:

137

Bravo

AF:

0.0635

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Ceroid lipofuscinosis, neuronal, 4 (Kufs type)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 22, 2015

- -

Neuronal Ceroid-Lipofuscinosis, Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neuronal ceroid lipofuscinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.63

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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