chr20-63895194-T-TGCCGCC

Position:

• chr20-63895194-T-TGCCGCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_025219.3(DNAJC5):​c.-125_-120dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 153,706 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (2 hom.)
• Consequence: DNAJC5 NM_025219.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 299 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-125_-120dup		5_prime_UTR_variant	1/5	ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-1810_-1805dup		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.-125_-120dup		5_prime_UTR_variant	1/5	1	NM_025219.3	ENSP00000354111	P1
DNAJC5	ENST00000470551.1	c.-125_-120dup		5_prime_UTR_variant, NMD_transcript_variant	1/6	2		ENSP00000434744

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 287 AN: 149082 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00419

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00180

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000629

Gnomad OTH AF: 0.00194

GnomAD4 exome AF: 0.00310 AC: 14 AN: 4522 Hom.: 2 Cov.: 0 AF XY: 0.00250 AC XY: 8 AN XY: 3202

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00356

Gnomad4 OTH exome AF: 0.00685

GnomAD4 genome AF: 0.00200 AC: 299 AN: 149184 Hom.: 3 Cov.: 31 AF XY: 0.00224 AC XY: 163 AN XY: 72744

Gnomad4 AFR AF: 0.00447

Gnomad4 AMR AF: 0.00180

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.000587

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.000629

Gnomad4 OTH AF: 0.00192

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neuronal Ceroid-Lipofuscinosis, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs531246320; hg19: chr20-62526547;