20-63919364-C-T

Position:

• chr20-63919364-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360864.9(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 ENST00000360864.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

LOC124904951 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LOC124904951	XM_047440634.1	c.-36C>T		5_prime_UTR_variant	1/1		XP_047296590.1
DNAJC5	NM_025219.3	c.-11-8971C>T		intron_variant		ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-11-8971C>T		intron_variant			XP_047296465.1
DNAJC5	XM_047440511.1	c.-12+1646C>T		intron_variant			XP_047296467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-8971C>T		intron_variant		1	NM_025219.3	ENSP00000354111	P1
DNAJC5	ENST00000470551.1	c.-11-8971C>T		intron_variant, NMD_transcript_variant		2		ENSP00000434744

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

Gnomad4 AFR exome AF: 0.474

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.792

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.228

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

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.313

Alfa AF: 0.250 Hom.: 1237

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2427555; hg19: chr20-62550717;