20-63915744-A-G

Variant names:

• chr20-63915744-A-G
• rs2427547
• NM_025219.3:c.-11-12591A>G

Variant summary

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

The ENST00000360864.9(DNAJC5):​c.-11-12591A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,108 control chromosomes in the GnomAD database, including 19,603 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 0.47 (19603 hom., cov: 33)
• Consequence: DNAJC5 ENST00000360864.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 1 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]

DNAJC5 Gene-Disease associations (from GenCC):

• ceroid lipofuscinosis, neuronal, 4 (Kufs type)

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• adult neuronal ceroid lipofuscinosis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000290226 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360864.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	NM_025219.3	MANE Select	c.-11-12591A>G		intron	N/A	NP_079495.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	ENST00000360864.9	TSL:1 MANE Select	c.-11-12591A>G		intron	N/A	ENSP00000354111.4
	DNAJC5	ENST00000470551.1	TSL:2	n.-11-12591A>G		intron	N/A	ENSP00000434744.1
	ENSG00000290226	ENST00000703636.1		n.454-12591A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70747 AN: 151990 Hom.: 19541 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.428

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.466 AC: 70874 AN: 152108 Hom.: 19603 Cov.: 33 AF XY: 0.471 AC XY: 35061 AN XY: 74368

African (AFR) AF: 0.714 AC: 29604 AN: 41482

American (AMR) AF: 0.500 AC: 7640 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3470

East Asian (EAS) AF: 0.942 AC: 4880 AN: 5180

South Asian (SAS) AF: 0.341 AC: 1643 AN: 4824

European-Finnish (FIN) AF: 0.414 AC: 4385 AN: 10582

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20329 AN: 67976

Other (OTH) AF: 0.433 AC: 916 AN: 2116

Alfa AF: 0.433 Hom.: 2369

Bravo AF: 0.490

Asia WGS AF: 0.650 AC: 2258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.40
PhyloP100		-1.3
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: rs2427547; hg19: chr20-62547097;