20-63929545-C-T

Variant names:

• chr20-63929545-C-T
• rs2295436
• NM_025219.3:c.321+20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025219.3(DNAJC5):​c.321+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,457,746 control chromosomes in the GnomAD database, including 2,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (539 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1808 hom.)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.15
• Publications: 3 publications found

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, Orphanet, Labcorp Genetics (formerly Invitae)
• adult neuronal ceroid lipofuscinosis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-63929545-C-T is Benign according to our data. Variant chr20-63929545-C-T is described in ClinVar as Benign. ClinVar VariationId is 137123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.321+20C>T		intron_variant	Intron 3 of 4	ENST00000360864.9	NP_079495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864.9	c.321+20C>T		intron_variant	Intron 3 of 4	1	NM_025219.3	ENSP00000354111.4
DNAJC5	ENST00000470551.1	n.321+20C>T		intron_variant	Intron 3 of 5	2		ENSP00000434744.1
DNAJC5	ENST00000703637.1	n.321+20C>T		intron_variant	Intron 3 of 5			ENSP00000515413.1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 11932 AN: 150812 Hom.: 539 Cov.: 31

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.0685

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0644

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0849

GnomAD2 exomes AF: 0.0298 AC: 6524 AN: 219044 AF XY: 0.0268

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.0294

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.0731

Gnomad FIN exome AF: 0.0434

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0326

GnomAD4 exome AF: 0.0307 AC: 40104 AN: 1306826 Hom.: 1808 Cov.: 32 AF XY: 0.0329 AC XY: 21478 AN XY: 653214

African (AFR) AF: 0.0329 AC: 991 AN: 30112

American (AMR) AF: 0.0382 AC: 1545 AN: 40436

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 1035 AN: 24252

East Asian (EAS) AF: 0.101 AC: 3800 AN: 37596

South Asian (SAS) AF: 0.0422 AC: 3383 AN: 80188

European-Finnish (FIN) AF: 0.0738 AC: 3734 AN: 50618

Middle Eastern (MID) AF: 0.0588 AC: 308 AN: 5236

European-Non Finnish (NFE) AF: 0.0233 AC: 22942 AN: 983368

Other (OTH) AF: 0.0430 AC: 2366 AN: 55020

GnomAD4 genome AF: 0.0791 AC: 11936 AN: 150920 Hom.: 539 Cov.: 31 AF XY: 0.0779 AC XY: 5749 AN XY: 73786

African (AFR) AF: 0.0782 AC: 3214 AN: 41074

American (AMR) AF: 0.0726 AC: 1103 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0685 AC: 236 AN: 3446

East Asian (EAS) AF: 0.128 AC: 653 AN: 5082

South Asian (SAS) AF: 0.0643 AC: 307 AN: 4776

European-Finnish (FIN) AF: 0.0814 AC: 855 AN: 10498

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0770 AC: 5201 AN: 67550

Other (OTH) AF: 0.0836 AC: 176 AN: 2106

Alfa AF: 0.0496 Hom.: 50

Bravo AF: 0.0836

Asia WGS AF: 0.0530 AC: 180 AN: 3380

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Dec 02, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jan 04, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Neuronal ceroid lipofuscinosis Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.97
DANN	Benign	0.73
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2295436; hg19: chr20-62560898;