dbSNP rs78457562: DNAJC5:c.322-10C>T (chr20-63930841-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025219.3(DNAJC5):c.322-10C>T variant causes a 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 intron

Scores

Splicing: ADA: 0.00001350

Clinical Significance

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

Conservation

PhyloP100: -0.529

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

ceroid lipofuscinosis, neuronal, 4 (Kufs type)
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
adult neuronal ceroid lipofuscinosis
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

DNAJC5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_025219.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 137124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	NM_025219.3	MANE Select	c.322-10C>T		intron	N/A	NP_079495.1	Q9H3Z4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJC5	ENST00000360864.9	TSL:1 MANE Select	c.322-10C>T	intron	N/A	ENSP00000354111.4	Q9H3Z4-1
DNAJC5	ENST00000898575.1		c.322-10C>T	intron	N/A	ENSP00000568634.1
DNAJC5	ENST00000898576.1		c.322-10C>T	intron	N/A	ENSP00000568635.1

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

GnomAD2 exomes

AF:

0.0654

AC:

16368

AN:

250390

AF XY:

0.0641

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 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

African (AFR)

AF:

0.0705

AC:

2355

AN:

33422

American (AMR)

AF:

0.0320

AC:

1432

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0445

AC:

1162

AN:

26128

East Asian (EAS)

AF:

0.00242

AC:

AN:

39700

South Asian (SAS)

AF:

0.0408

AC:

3513

AN:

86180

European-Finnish (FIN)

AF:

0.175

AC:

9251

AN:

52920

Middle Eastern (MID)

AF:

0.0294

AC:

135

AN:

4586

European-Non Finnish (NFE)

AF:

0.0751

AC:

83451

AN:

1111836

Other (OTH)

AF:

0.0681

AC:

4103

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

6355

12710

19064

25419

31774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3012

6024

9036

12048

15060

<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

AF:

0.0745

AC:

11344

AN:

152318

Hom.:

532

Cov.:

AF XY:

0.0775

AC XY:

5770

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0685

AC:

2850

AN:

41576

American (AMR)

AF:

0.0470

AC:

719

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3472

East Asian (EAS)

AF:

0.00328

AC:

AN:

5190

South Asian (SAS)

AF:

0.0340

AC:

164

AN:

4830

European-Finnish (FIN)

AF:

0.175

AC:

1851

AN:

10604

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0792

AC:

5387

AN:

68026

Other (OTH)

AF:

0.0653

AC:

138

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

542

1084

1627

2169

2711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0749

Hom.:

137

Bravo

AF:

0.0635

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Ceroid lipofuscinosis, neuronal, 4 (Kufs type) (1)

Neuronal ceroid lipofuscinosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.63

(source)

DANN

Benign

0.56

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over