20-63895448-G-C

Position:

• chr20-63895448-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_025219.3(DNAJC5):​c.-12+125G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 147,384 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (392 hom., cov: 31)
  • Exomes 𝑓: 0.10 (6 hom.)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.870

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-63895448-G-C is Benign according to our data. Variant chr20-63895448-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1202208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-12+125G>C		intron_variant		ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-1572G>C		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+125G>C		intron_variant		1	NM_025219.3	ENSP00000354111	P1
DNAJC5	ENST00000470551.1	c.-12+125G>C		intron_variant, NMD_transcript_variant		2		ENSP00000434744

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7620 AN: 146456 Hom.: 387 Cov.: 31

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0174

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0450

GnomAD4 exome AF: 0.104 AC: 86 AN: 824 Hom.: 6 AF XY: 0.120 AC XY: 49 AN XY: 408

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0521 AC: 7643 AN: 146560 Hom.: 392 Cov.: 31 AF XY: 0.0578 AC XY: 4122 AN XY: 71332

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0174

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0985

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0490

Alfa AF: 0.0442 Hom.: 33

Bravo AF: 0.0494

Asia WGS AF: 0.156 AC: 364 AN: 2344

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.7
DANN	Benign	0.42
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.7

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: rs543059118; hg19: chr20-62526801;