rs7268785

Variant names:

• chr20-63919453-G-C
• rs7268785
• NM_025219.3:c.-11-8882G>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_025219.3(DNAJC5):​c.-11-8882G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 117,358 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0011 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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:):

MIR941-1 (HGNC:33684): (microRNA 941-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR941-2 (HGNC:33685): (microRNA 941-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR941-3 (HGNC:33686): (microRNA 941-3) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS2: High AC in GnomAd4 at 130 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-11-8882G>C		intron_variant	Intron 1 of 4	ENST00000360864.9	NP_079495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-8882G>C		intron_variant	Intron 1 of 4	1	NM_025219.3	ENSP00000354111.4

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 130 AN: 117268 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00299

Gnomad AMR AF: 0.00104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000537

Gnomad SAS AF: 0.00315

Gnomad FIN AF: 0.00121

Gnomad MID AF: 0.0111

Gnomad NFE AF: 0.000757

Gnomad OTH AF: 0.00190

GnomAD3 exomes AF: 0.00139 AC: 292 AN: 209670 Hom.: 0 AF XY: 0.00117 AC XY: 135 AN XY: 115774

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00262

Gnomad ASJ exome AF: 0.000331

Gnomad EAS exome AF: 0.00214

Gnomad SAS exome AF: 0.00164

Gnomad FIN exome AF: 0.000451

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.00259

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00146 AC: 487 AN: 334146 Hom.: 0 Cov.: 0 AF XY: 0.00130 AC XY: 252 AN XY: 193300

Gnomad4 AFR exome AF: 0.00228

Gnomad4 AMR exome AF: 0.00327

Gnomad4 ASJ exome AF: 0.000642

Gnomad4 EAS exome AF: 0.00878

Gnomad4 SAS exome AF: 0.00151

Gnomad4 FIN exome AF: 0.000295

Gnomad4 NFE exome AF: 0.000773

Gnomad4 OTH exome AF: 0.00121

GnomAD4 genome AF: 0.00111 AC: 130 AN: 117358 Hom.: 0 Cov.: 24 AF XY: 0.00121 AC XY: 69 AN XY: 56926

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00104

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000537

Gnomad4 SAS AF: 0.00315

Gnomad4 FIN AF: 0.00121

Gnomad4 NFE AF: 0.000757

Gnomad4 OTH AF: 0.00188

Alfa AF: 0.00269 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.8
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7268785; hg19: chr20-62550806; COSMIC: COSV62671628; COSMIC: COSV62671628;