20-63929545-C-T

Position:

• chr20-63929545-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025219.3(DNAJC5):​c.321+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,457,746 control chromosomes in the GnomAD database, including 2,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (539 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1808 hom.)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.15

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-63929545-C-T is Benign according to our data. Variant chr20-63929545-C-T is described in ClinVar as [Benign]. Clinvar id is 137123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63929545-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.321+20C>T		intron_variant		ENST00000360864.9	NP_079495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864.9	c.321+20C>T		intron_variant		1	NM_025219.3	ENSP00000354111.4
DNAJC5	ENST00000470551.1	n.321+20C>T		intron_variant		2		ENSP00000434744.1
DNAJC5	ENST00000703637.1	n.321+20C>T		intron_variant				ENSP00000515413.1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 11932 AN: 150812 Hom.: 539 Cov.: 31

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.0685

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0644

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0849

GnomAD3 exomes AF: 0.0298 AC: 6524 AN: 219044 Hom.: 331 AF XY: 0.0268 AC XY: 3180 AN XY: 118458

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.0294

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.0731

Gnomad SAS exome AF: 0.0165

Gnomad FIN exome AF: 0.0434

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0326

GnomAD4 exome AF: 0.0307 AC: 40104 AN: 1306826 Hom.: 1808 Cov.: 32 AF XY: 0.0329 AC XY: 21478 AN XY: 653214

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.0382

Gnomad4 ASJ exome AF: 0.0427

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0422

Gnomad4 FIN exome AF: 0.0738

Gnomad4 NFE exome AF: 0.0233

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome AF: 0.0791 AC: 11936 AN: 150920 Hom.: 539 Cov.: 31 AF XY: 0.0779 AC XY: 5749 AN XY: 73786

Gnomad4 AFR AF: 0.0782

Gnomad4 AMR AF: 0.0726

Gnomad4 ASJ AF: 0.0685

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0643

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0836

Alfa AF: 0.0487 Hom.: 48

Bravo AF: 0.0836

Asia WGS AF: 0.0530 AC: 180 AN: 3380

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Jan 04, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neuronal ceroid lipofuscinosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.97
DANN	Benign	0.73

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: rs2295436; hg19: chr20-62560898;