rs2427556

Positions:

• chr20-63919471-G-A
• chr20-63919471-G-C
• chr20-63919471-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025219.3(DNAJC5):​c.-11-8864G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (2979 hom., cov: 18)
  • Exomes 𝑓: 0.086 (811 hom.)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

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]

LOC124904951 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-11-8864G>A		intron_variant		ENST00000360864.9	NP_079495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-8864G>A		intron_variant		1	NM_025219.3	ENSP00000354111.4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 25107 AN: 108846 Hom.: 2969 Cov.: 18

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.116

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.0289 AC: 3374 AN: 116620 Hom.: 219 AF XY: 0.0226 AC XY: 1507 AN XY: 66712

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.0698

Gnomad ASJ exome AF: 0.0121

Gnomad EAS exome AF: 0.257

Gnomad SAS exome AF: 0.00806

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0225

GnomAD4 exome AF: 0.0863 AC: 18896 AN: 219064 Hom.: 811 Cov.: 0 AF XY: 0.0854 AC XY: 11013 AN XY: 128956

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.0394

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0912

Gnomad4 NFE exome AF: 0.0678

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.231 AC: 25136 AN: 108906 Hom.: 2979 Cov.: 18 AF XY: 0.235 AC XY: 12213 AN XY: 51956

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.219

Alfa AF: 0.256 Hom.: 266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs2427556; hg19: chr20-62550824; COSMIC: COSV62670637; COSMIC: COSV62670637;