chr20-63919471-G-A

Variant names:

• chr20-63919471-G-A
• rs2427556
• NM_025219.3:c.-11-8864G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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]

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-11-8864G>A		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.-11-8864G>A		intron_variant	Intron 1 of 4	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

GnomAD2 exomes AF: 0.0289 AC: 3374 AN: 116620 AF XY: 0.0226

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.166 AC: 591 AN: 3564

American (AMR) AF: 0.119 AC: 1261 AN: 10592

Ashkenazi Jewish (ASJ) AF: 0.0394 AC: 303 AN: 7688

East Asian (EAS) AF: 0.486 AC: 1319 AN: 2712

South Asian (SAS) AF: 0.105 AC: 4745 AN: 45054

European-Finnish (FIN) AF: 0.0912 AC: 857 AN: 9396

Middle Eastern (MID) AF: 0.0610 AC: 55 AN: 902

European-Non Finnish (NFE) AF: 0.0678 AC: 8760 AN: 129136

Other (OTH) AF: 0.100 AC: 1005 AN: 10020

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.367 AC: 9516 AN: 25914

American (AMR) AF: 0.294 AC: 3065 AN: 10436

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 464 AN: 2948

East Asian (EAS) AF: 0.655 AC: 1595 AN: 2436

South Asian (SAS) AF: 0.179 AC: 585 AN: 3266

European-Finnish (FIN) AF: 0.193 AC: 1260 AN: 6526

Middle Eastern (MID) AF: 0.118 AC: 28 AN: 238

European-Non Finnish (NFE) AF: 0.149 AC: 8164 AN: 54964

Other (OTH) AF: 0.219 AC: 330 AN: 1508

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
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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