chr20-63919364-C-T

Variant names:

• chr20-63919364-C-T
• rs2427555
• NM_025219.3:c.-11-8971C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025219.3(DNAJC5):​c.-11-8971C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 448,418 control chromosomes in the GnomAD database, including 22,629 homozygotes. 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 0.33 (9889 hom., cov: 33)
  • Exomes 𝑓: 0.23 (12740 hom.)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 10 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:):

MIR941-2 (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]

MIR941-1 (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]

MIR941-3 (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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-11-8971C>T		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.-11-8971C>T		intron_variant	Intron 1 of 4	1	NM_025219.3	ENSP00000354111.4

Frequencies

GnomAD3 genomes AF: 0.331 AC: 48294 AN: 145800 Hom.: 9857 Cov.: 33

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.228 AC: 68927 AN: 302522 Hom.: 12740 AF XY: 0.215 AC XY: 37295 AN XY: 173324

African (AFR) AF: 0.474 AC: 4294 AN: 9056

American (AMR) AF: 0.440 AC: 11797 AN: 26790

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 1759 AN: 10520

East Asian (EAS) AF: 0.792 AC: 8362 AN: 10552

South Asian (SAS) AF: 0.202 AC: 11546 AN: 57066

European-Finnish (FIN) AF: 0.196 AC: 2331 AN: 11890

Middle Eastern (MID) AF: 0.155 AC: 179 AN: 1152

European-Non Finnish (NFE) AF: 0.158 AC: 25492 AN: 161596

Other (OTH) AF: 0.228 AC: 3167 AN: 13900

GnomAD4 genome AF: 0.332 AC: 48370 AN: 145896 Hom.: 9889 Cov.: 33 AF XY: 0.338 AC XY: 24042 AN XY: 71050

African (AFR) AF: 0.483 AC: 19479 AN: 40316

American (AMR) AF: 0.399 AC: 5829 AN: 14616

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 704 AN: 3390

East Asian (EAS) AF: 0.807 AC: 3912 AN: 4850

South Asian (SAS) AF: 0.258 AC: 1180 AN: 4580

European-Finnish (FIN) AF: 0.297 AC: 2827 AN: 9510

Middle Eastern (MID) AF: 0.162 AC: 46 AN: 284

European-Non Finnish (NFE) AF: 0.207 AC: 13519 AN: 65442

Other (OTH) AF: 0.313 AC: 635 AN: 2028

Alfa AF: 0.247 Hom.: 2252

Bravo AF: 0.362

Asia WGS AF: 0.473 AC: 1392 AN: 2950

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.54
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs2427555; hg19: chr20-62550717;