20-63895147-T-TCCGCTG

Position:

• chr20-63895147-T-TCCGCTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_025219.3(DNAJC5):​c.-166_-161dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 154,148 control chromosomes in the GnomAD database, including 53 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (51 hom., cov: 32)
  • Exomes 𝑓: 0.012 (2 hom.)
• Consequence: DNAJC5 NM_025219.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.229

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 -10 ACMG points.

• BP6: Variant 20-63895147-T-TCCGCTG is Benign according to our data. Variant chr20-63895147-T-TCCGCTG is described in ClinVar as [Likely_benign]. Clinvar id is 339345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0186 (2810/151166) while in subpopulation AFR AF= 0.0462 (1911/41372). AF 95% confidence interval is 0.0445. There are 51 homozygotes in gnomad4. There are 1355 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2810 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-166_-161dup		5_prime_UTR_variant	1/5	ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-1851_-1846dup		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.-166_-161dup		5_prime_UTR_variant	1/5	1	NM_025219.3	ENSP00000354111	P1
DNAJC5	ENST00000470551.1			upstream_gene_variant		2		ENSP00000434744

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2805 AN: 151058 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.00983

Gnomad ASJ AF: 0.00782

Gnomad EAS AF: 0.00930

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.00486

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.0149

GnomAD4 exome AF: 0.0121 AC: 36 AN: 2982 Hom.: 2 Cov.: 0 AF XY: 0.0113 AC XY: 23 AN XY: 2038

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00820

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00783

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0186 AC: 2810 AN: 151166 Hom.: 51 Cov.: 32 AF XY: 0.0183 AC XY: 1355 AN XY: 73876

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.00782

Gnomad4 EAS AF: 0.00932

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.00486

Gnomad4 NFE AF: 0.00717

Gnomad4 OTH AF: 0.0148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neuronal Ceroid-Lipofuscinosis, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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: rs563818595; hg19: chr20-62526500;