20-63895194-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCC

Variant names:

• chr20-63895194-T-TGCC
• rs531246320
• NM_025219.3:c.-122_-120dupGCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_025219.3(DNAJC5):​c.-122_-120dupGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 153,670 control chromosomes in the GnomAD database, including 649 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (576 hom., cov: 31)
  • Exomes 𝑓: 0.16 (73 hom.)
• Consequence: DNAJC5 NM_025219.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.75
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 20-63895194-T-TGCC is Benign according to our data. Variant chr20-63895194-T-TGCC is described in ClinVar as Benign. ClinVar VariationId is 339350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 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.-122_-120dupGCC		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.-122_-120dupGCC		5_prime_UTR	Exon 1 of 5	ENSP00000354111.4	Q9H3Z4-1
	DNAJC5	ENST00000898575.1		c.-117_-115dupGCC		5_prime_UTR	Exon 1 of 5	ENSP00000568634.1
	DNAJC5	ENST00000921989.1		c.-34_-32dupGCC		5_prime_UTR	Exon 1 of 5	ENSP00000592048.1

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12277 AN: 149052 Hom.: 575 Cov.: 31

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.0859

GnomAD4 exome AF: 0.164 AC: 741 AN: 4516 Hom.: 73 Cov.: 0 AF XY: 0.172 AC XY: 550 AN XY: 3196

African (AFR) AF: 0.217 AC: 13 AN: 60

American (AMR) AF: 0.0750 AC: 3 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 6 AN: 36

East Asian (EAS) AF: 0.272 AC: 55 AN: 202

South Asian (SAS) AF: 0.0722 AC: 65 AN: 900

European-Finnish (FIN) AF: 0.147 AC: 5 AN: 34

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.183 AC: 564 AN: 3088

Other (OTH) AF: 0.208 AC: 30 AN: 144

GnomAD4 genome AF: 0.0824 AC: 12287 AN: 149154 Hom.: 576 Cov.: 31 AF XY: 0.0816 AC XY: 5931 AN XY: 72728

African (AFR) AF: 0.0891 AC: 3667 AN: 41146

American (AMR) AF: 0.0773 AC: 1162 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 218 AN: 3412

East Asian (EAS) AF: 0.130 AC: 666 AN: 5114

South Asian (SAS) AF: 0.0652 AC: 313 AN: 4800

European-Finnish (FIN) AF: 0.0801 AC: 768 AN: 9592

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0768 AC: 5126 AN: 66780

Other (OTH) AF: 0.0845 AC: 176 AN: 2082

Alfa AF: 0.0201 Hom.: 12

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neuronal Ceroid-Lipofuscinosis, Recessive (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
Mutation Taster		=298/2	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs531246320; hg19: chr20-62526547;