Genetic Variant DNAJC5:c.-128_-120dupGCCGCCGCC (chr20-63895194-T-TGCCGCCGCC) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_025219.3(DNAJC5):c.-128_-120dupGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 153,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

DNAJC5
NM_025219.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.75

Publications

1 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: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
adult neuronal ceroid lipofuscinosis
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

DNAJC5 links:

ENSG00000290226 (HGNC:):

ENSG00000290226 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 20-63895194-T-TGCCGCCGCC is Benign according to our data. Variant chr20-63895194-T-TGCCGCCGCC is described in ClinVar as Benign. ClinVar VariationId is 2652561.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 75 AD gene.

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.-128_-120dupGCCGCCGCC		5_prime_UTR	Exon 1 of 5	NP_079495.1	Q9H3Z4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJC5	ENST00000360864.9	TSL:1 MANE Select	c.-128_-120dupGCCGCCGCC	5_prime_UTR	Exon 1 of 5	ENSP00000354111.4	Q9H3Z4-1
DNAJC5	ENST00000898575.1		c.-123_-115dupGCCGCCGCC	5_prime_UTR	Exon 1 of 5	ENSP00000568634.1
DNAJC5	ENST00000921989.1		c.-40_-32dupGCCGCCGCC	5_prime_UTR	Exon 1 of 5	ENSP00000592048.1

Frequencies

GnomAD3 genomes

AF:

0.000503

AC:

AN:

149082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000533

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.00175

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000464

Gnomad OTH

AF:

0.000485

GnomAD4 exome

AF:

0.00133

AC:

AN:

4520

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

3202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00495

AC:

AN:

202

South Asian (SAS)

AF:

0.00

AC:

AN:

900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00162

AC:

AN:

3090

Other (OTH)

AF:

0.00

AC:

AN:

146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.808

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000503

AC:

AN:

149184

Hom.:

Cov.:

AF XY:

0.000522

AC XY:

AN XY:

72744

show subpopulations

African (AFR)

AF:

0.000146

AC:

AN:

41156

American (AMR)

AF:

0.000532

AC:

AN:

15036

Ashkenazi Jewish (ASJ)

AF:

0.000293

AC:

AN:

3412

East Asian (EAS)

AF:

0.00176

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

9594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000464

AC:

AN:

66792

Other (OTH)

AF:

0.000480

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000430

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.7

Mutation Taster

=298/2

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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20-63895194-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over