chr20-63895366-G-A

Position:

• chr20-63895366-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+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 146,496 control chromosomes in the GnomAD database, including 571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (569 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2 hom.)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.127

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=-0.86).
• BP6: Variant 20-63895366-G-A is Benign according to our data. Variant chr20-63895366-G-A is described in ClinVar as [Benign]. Clinvar id is 1228738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-12+43G>A		intron_variant		ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-1654G>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+43G>A		intron_variant		1	NM_025219.3	ENSP00000354111	P1
DNAJC5	ENST00000470551.1	c.-12+43G>A		intron_variant, NMD_transcript_variant		2		ENSP00000434744

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12173 AN: 145840 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0653

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.0866

GnomAD4 exome AF: 0.101 AC: 56 AN: 556 Hom.: 2 Cov.: 0 AF XY: 0.0922 AC XY: 26 AN XY: 282

Gnomad4 SAS exome AF: 0.101

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0835 AC: 12186 AN: 145940 Hom.: 569 Cov.: 32 AF XY: 0.0828 AC XY: 5883 AN XY: 71018

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.0780

Gnomad4 ASJ AF: 0.0653

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.0848

Gnomad4 NFE AF: 0.0777

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.0801 Hom.: 62

Asia WGS AF: 0.0770 AC: 189 AN: 2440

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 24, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.96

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: rs185056589; hg19: chr20-62526719;