20-63919846-T-C

Variant names:

• chr20-63919846-T-C
• rs7360929
• NM_025219.3:c.-11-8489T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025219.3(DNAJC5):​c.-11-8489T>C 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00025 (8 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.00
• Publications: 6 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:):

MIR941-5 (HGNC:50845): (microRNA 941-5) 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]

MIR941-4 (HGNC:33687): (microRNA 941-4) 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	NM_025219.3	MANE Select	c.-11-8489T>C		intron	N/A	NP_079495.1	Q9H3Z4-1
	MIR941-5	NR_128719.1		n.-22T>C		upstream_gene	N/A
	MIR941-3	NR_030639.3		n.*214T>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	ENST00000360864.9	TSL:1 MANE Select	c.-11-8489T>C		intron	N/A	ENSP00000354111.4	Q9H3Z4-1
	DNAJC5	ENST00000898575.1		c.-6-8494T>C		intron	N/A	ENSP00000568634.1
	DNAJC5	ENST00000898576.1		c.-11-8489T>C		intron	N/A	ENSP00000568635.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 4030 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000776 AC: 11 AN: 141712 AF XY: 0.0000367

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000222

Gnomad FIN exome AF: 0.000150

Gnomad NFE exome AF: 0.0000826

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000251 AC: 55 AN: 219210 Hom.: 8 Cov.: 0 AF XY: 0.000209 AC XY: 27 AN XY: 129256

African (AFR) AF: 0.00 AC: 0 AN: 5318

American (AMR) AF: 0.000181 AC: 3 AN: 16548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8448

East Asian (EAS) AF: 0.00 AC: 0 AN: 3002

South Asian (SAS) AF: 0.000286 AC: 14 AN: 48870

European-Finnish (FIN) AF: 0.000218 AC: 2 AN: 9166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 886

European-Non Finnish (NFE) AF: 0.000281 AC: 33 AN: 117230

Other (OTH) AF: 0.000308 AC: 3 AN: 9742

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4032 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1944

African (AFR) AF: 0.00 AC: 0 AN: 522

American (AMR) AF: 0.00 AC: 0 AN: 264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 208

East Asian (EAS) AF: 0.00 AC: 0 AN: 34

South Asian (SAS) AF: 0.00 AC: 0 AN: 58

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 86

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2802

Other (OTH) AF: 0.00 AC: 0 AN: 42

Alfa AF: 0.0216 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.0
DANN	Benign	0.18
PhyloP100		-7.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7360929;

hg19: chr20-62551199;