20-63895274-A-AGCGGAGCC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_025219.3(DNAJC5):c.-51_-44dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00976 in 146,394 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAJC5 NM_025219.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.257

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 -6 ACMG points.

• BP6: Variant 20-63895274-A-AGCGGAGCC is Benign according to our data. Variant chr20-63895274-A-AGCGGAGCC is described in ClinVar as [Likely_benign]. Clinvar id is 418748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1430 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC5	NM_025219.3	c.-51_-44dup		5_prime_UTR_variant	1/5	ENST00000360864.9
DNAJC5	XM_047440509.1	c.-1736_-1729dup		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-51_-44dup		5_prime_UTR_variant	1/5	1	NM_025219.3	P1
DNAJC5	ENST00000470551.1	c.-51_-44dup		5_prime_UTR_variant, NMD_transcript_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.00977 AC: 1430 AN: 146302 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00384

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.00672

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0104

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 870 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 424

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00976 AC: 1429 AN: 146394 Hom.: 8 Cov.: 32 AF XY: 0.00930 AC XY: 663 AN XY: 71310

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00384

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.00672

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.0103

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 05, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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: rs1345043761; hg19: chr20-62526627;