chr20-63918212-G-A

Variant names:

• chr20-63918212-G-A
• rs2427554
• NM_025219.3:c.-11-10123G>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.-11-10123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,892 control chromosomes in the GnomAD database, including 10,692 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 0.34 (10692 hom., cov: 32)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• Publications: 12 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

LOC124904951 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	NM_025219.3	MANE Select	c.-11-10123G>A		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.-11-10123G>A		intron	N/A	ENSP00000354111.4
	DNAJC5	ENST00000470551.1	TSL:2	n.-11-10123G>A		intron	N/A	ENSP00000434744.1
	ENSG00000290226	ENST00000703636.1		n.454-10123G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52095 AN: 151774 Hom.: 10655 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.344 AC: 52187 AN: 151892 Hom.: 10692 Cov.: 32 AF XY: 0.352 AC XY: 26114 AN XY: 74220

African (AFR) AF: 0.488 AC: 20196 AN: 41400

American (AMR) AF: 0.410 AC: 6255 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 747 AN: 3472

East Asian (EAS) AF: 0.810 AC: 4173 AN: 5154

South Asian (SAS) AF: 0.274 AC: 1316 AN: 4802

European-Finnish (FIN) AF: 0.331 AC: 3493 AN: 10558

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15014 AN: 67948

Other (OTH) AF: 0.325 AC: 686 AN: 2114

Alfa AF: 0.264 Hom.: 24700

Bravo AF: 0.361

Asia WGS AF: 0.553 AC: 1921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2427554; hg19: chr20-62549565;