20-63895343-G-A

Position:

• chr20-63895343-G-A

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.-12+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 147,356 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (39 hom., cov: 32)
  • Exomes 𝑓: 0.080 (4 hom.)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.414

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=-0.87).
• BP6: Variant 20-63895343-G-A is Benign according to our data. Variant chr20-63895343-G-A is described in ClinVar as [Benign]. Clinvar id is 379279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-12+20G>A		intron_variant		ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-1677G>A		5_prime_UTR_variant	1/5		XP_047296465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-12+20G>A		intron_variant		1	NM_025219.3	ENSP00000354111	P1
DNAJC5	ENST00000470551.1	c.-12+20G>A		intron_variant, NMD_transcript_variant		2		ENSP00000434744

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1922 AN: 146386 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00509

Gnomad ASJ AF: 0.0439

Gnomad EAS AF: 0.000776

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0104

GnomAD4 exome AF: 0.0805 AC: 70 AN: 870 Hom.: 4 Cov.: 0 AF XY: 0.0873 AC XY: 37 AN XY: 424

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.0837

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0131 AC: 1918 AN: 146486 Hom.: 39 Cov.: 32 AF XY: 0.0158 AC XY: 1126 AN XY: 71308

Gnomad4 AFR AF: 0.00257

Gnomad4 AMR AF: 0.00508

Gnomad4 ASJ AF: 0.0439

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.00983

Alfa AF: 0.0126 Hom.: 6

Bravo AF: 0.00869

Asia WGS AF: 0.0230 AC: 60 AN: 2608

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 05, 2016

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.6
DANN	Benign	0.97
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs560162132; hg19: chr20-62526696;