ENST00000360864:c.-166_-161dupCTGCCG

Variant names:

• chr20-63895147-T-TCCGCTG
• rs563818595
• NM_025219.3:c.-166_-161dupCTGCCG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000360864.9(DNAJC5):​c.-166_-161dupCTGCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 154,148 control chromosomes in the GnomAD database, including 53 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (51 hom., cov: 32)
  • Exomes 𝑓: 0.012 (2 hom.)
• Consequence: DNAJC5 ENST00000360864.9 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.229
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• adult neuronal ceroid lipofuscinosis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000290226 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-63895147-T-TCCGCTG is Benign according to our data. Variant chr20-63895147-T-TCCGCTG is described in ClinVar as Likely_benign. ClinVar VariationId is 339345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0186 (2810/151166) while in subpopulation AFR AF = 0.0462 (1911/41372). AF 95% confidence interval is 0.0445. There are 51 homozygotes in GnomAd4. There are 1355 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2810 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360864.9. 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.-166_-161dupCTGCCG		5_prime_UTR	Exon 1 of 5	NP_079495.1	Q9H3Z4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	ENST00000360864.9	TSL:1 MANE Select	c.-166_-161dupCTGCCG		5_prime_UTR	Exon 1 of 5	ENSP00000354111.4	Q9H3Z4-1
	DNAJC5	ENST00000898575.1		c.-161_-156dupCTGCCG		5_prime_UTR	Exon 1 of 5	ENSP00000568634.1
	DNAJC5	ENST00000921989.1		c.-78_-73dupCTGCCG		5_prime_UTR	Exon 1 of 5	ENSP00000592048.1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2805 AN: 151058 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.00983

Gnomad ASJ AF: 0.00782

Gnomad EAS AF: 0.00930

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.00486

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.0149

GnomAD4 exome AF: 0.0121 AC: 36 AN: 2982 Hom.: 2 Cov.: 0 AF XY: 0.0113 AC XY: 23 AN XY: 2038

African (AFR) AF: 0.0769 AC: 2 AN: 26

American (AMR) AF: 0.00 AC: 0 AN: 26

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14

East Asian (EAS) AF: 0.00820 AC: 1 AN: 122

South Asian (SAS) AF: 0.0193 AC: 17 AN: 880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.00783 AC: 14 AN: 1788

Other (OTH) AF: 0.0217 AC: 2 AN: 92

GnomAD4 genome AF: 0.0186 AC: 2810 AN: 151166 Hom.: 51 Cov.: 32 AF XY: 0.0183 AC XY: 1355 AN XY: 73876

African (AFR) AF: 0.0462 AC: 1911 AN: 41372

American (AMR) AF: 0.00981 AC: 149 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00782 AC: 27 AN: 3454

East Asian (EAS) AF: 0.00932 AC: 48 AN: 5148

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4822

European-Finnish (FIN) AF: 0.00486 AC: 50 AN: 10290

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00717 AC: 485 AN: 67596

Other (OTH) AF: 0.0148 AC: 31 AN: 2100

Alfa AF: 0.00200 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Neuronal Ceroid-Lipofuscinosis, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs563818595; hg19: chr20-62526500;