20-63895147-TCCGCTGCCGCTGCCGCTG-TCCGCTGCCGCTGCCGCTGCCGCTGCCGCTG

Variant names:

• chr20-63895147-T-TCCGCTGCCGCTG
• rs563818595
• NM_025219.3:c.-172_-161dupCTGCCGCTGCCG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_025219.3(DNAJC5):​c.-172_-161dupCTGCCGCTGCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 154,158 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (0 hom.)
• Consequence: DNAJC5 NM_025219.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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]

ENSG00000290226 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 651 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-172_-161dupCTGCCGCTGCCG		5_prime_UTR_variant	Exon 1 of 5	ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-1857_-1846dupCTGCCGCTGCCG		5_prime_UTR_variant	Exon 1 of 5		XP_047296465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864	c.-172_-161dupCTGCCGCTGCCG		5_prime_UTR_variant	Exon 1 of 5	1	NM_025219.3	ENSP00000354111.4
ENSG00000290226	ENST00000703636.1	n.453+12343_453+12354dupCTGCCGCTGCCG		intron_variant	Intron 4 of 4
DNAJC5	ENST00000470551.1	n.-188_-187insCCGCTGCCGCTG		upstream_gene_variant		2		ENSP00000434744.1

Frequencies

GnomAD3 genomes AF: 0.00430 AC: 650 AN: 151068 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00547

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00459

Gnomad OTH AF: 0.00962

GnomAD4 exome AF: 0.00469 AC: 14 AN: 2982 Hom.: 0 Cov.: 0 AF XY: 0.00442 AC XY: 9 AN XY: 2038

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00455

Gnomad4 FIN exome AF: 0.0357

Gnomad4 NFE exome AF: 0.00503

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00431 AC: 651 AN: 151176 Hom.: 4 Cov.: 32 AF XY: 0.00460 AC XY: 340 AN XY: 73880

Gnomad4 AFR AF: 0.00210

Gnomad4 AMR AF: 0.00547

Gnomad4 ASJ AF: 0.00347

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.00459

Gnomad4 OTH AF: 0.00952

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs563818595; hg19: chr20-62526500;