20-63895194-T-TGCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_025219.3(DNAJC5):c.-122_-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 0.0848 in 153,670 control chromosomes in the GnomAD database, including 649 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (576 hom., cov: 31)
  • Exomes 𝑓: 0.16 (73 hom.)
• Consequence: DNAJC5 NM_025219.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -16 ACMG points.

• BP6: Variant 20-63895194-T-TGCC is Benign according to our data. Variant chr20-63895194-T-TGCC is described in ClinVar as [Benign]. Clinvar id is 339350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC5	NM_025219.3	c.-122_-120dup		5_prime_UTR_variant	1/5	ENST00000360864.9
DNAJC5	XM_047440509.1	c.-1807_-1805dup		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-122_-120dup		5_prime_UTR_variant	1/5	1	NM_025219.3	P1
DNAJC5	ENST00000470551.1	c.-122_-120dup		5_prime_UTR_variant, NMD_transcript_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12277 AN: 149052 Hom.: 575 Cov.: 31

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.0859

GnomAD4 exome AF: 0.164 AC: 741 AN: 4516 Hom.: 73 Cov.: 0 AF XY: 0.172 AC XY: 550 AN XY: 3196

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.0750

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.0722

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.0824 AC: 12287 AN: 149154 Hom.: 576 Cov.: 31 AF XY: 0.0816 AC XY: 5931 AN XY: 72728

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.0773

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0652

Gnomad4 FIN AF: 0.0801

Gnomad4 NFE AF: 0.0768

Gnomad4 OTH AF: 0.0845

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 29, 2020

- -

Neuronal Ceroid-Lipofuscinosis, Recessive Benign:1

Benign, 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;