rs35544770

Variant names:

• chr20-63919919-G-A
• rs35544770
• NM_025219.3:c.-11-8416G>A

Variant summary

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

The NM_025219.3(DNAJC5):​c.-11-8416G>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 0.0 (0 hom., cov: 4)
  • Exomes 𝑓: 0.0000045 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• Publications: 7 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-11-8416G>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.-11-8416G>A		intron_variant	Intron 1 of 4	1	NM_025219.3	ENSP00000354111.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 19040 Hom.: 0 Cov.: 4

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

GnomAD4 exome AF: 0.00000445 AC: 1 AN: 224500 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 130096

African (AFR) AF: 0.00 AC: 0 AN: 4588

American (AMR) AF: 0.00 AC: 0 AN: 12128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7334

East Asian (EAS) AF: 0.00 AC: 0 AN: 3220

South Asian (SAS) AF: 0.00 AC: 0 AN: 48624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 900

European-Non Finnish (NFE) AF: 0.00000783 AC: 1 AN: 127692

Other (OTH) AF: 0.00 AC: 0 AN: 10500

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 19040 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 9382

African (AFR) AF: 0.00 AC: 0 AN: 2344

American (AMR) AF: 0.00 AC: 0 AN: 1970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 854

East Asian (EAS) AF: 0.00 AC: 0 AN: 188

South Asian (SAS) AF: 0.00 AC: 0 AN: 634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 48

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 11490

Other (OTH) AF: 0.00 AC: 0 AN: 276

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	0.82
PhyloP100		-3.3

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: rs35544770; hg19: chr20-62551272; COSMIC: COSV62670641; COSMIC: COSV62670641;