rs6089780

Positions:

• chr20-63919527-G-A
• chr20-63919527-G-C

Variant summary

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

The NM_025219.3(DNAJC5):​c.-11-8808G>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 0.11 (841 hom., cov: 7)
  • Exomes 𝑓: 0.035 (260 hom.)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-11-8808G>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.-11-8808G>A		intron_variant		1	NM_025219.3	ENSP00000354111.4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 6106 AN: 56912 Hom.: 836 Cov.: 7

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0481

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.0743 AC: 2394 AN: 32222 Hom.: 111 AF XY: 0.0693 AC XY: 1143 AN XY: 16486

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.0520

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.0291

Gnomad FIN exome AF: 0.0164

Gnomad NFE exome AF: 0.0359

Gnomad OTH exome AF: 0.0541

GnomAD4 exome AF: 0.0350 AC: 4885 AN: 139554 Hom.: 260 Cov.: 0 AF XY: 0.0344 AC XY: 2661 AN XY: 77426

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.0569

Gnomad4 ASJ exome AF: 0.0528

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.0216

Gnomad4 FIN exome AF: 0.0263

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0474

GnomAD4 genome AF: 0.107 AC: 6117 AN: 56936 Hom.: 841 Cov.: 7 AF XY: 0.110 AC XY: 2899 AN XY: 26358

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.0505

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.89

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: rs6089780; hg19: chr20-62550880; COSMIC: COSV62671019; COSMIC: COSV62671019;