Variant 20-63895274-A-AGCGGAGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_025219.3(DNAJC5):c.-51_-44dupCGGAGCCG 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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.257

Variant links:

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]

DNAJC5 links:

ENSG00000290226 (HGNC:):

ENSG00000290226 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 1429 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC5	NM_025219.3 link	c.-51_-44dupCGGAGCCG		5_prime_UTR_variant	Exon 1 of 5	ENST00000360864.9	NP_079495.1	Q9H3Z4-1Q6AHX3
DNAJC5	XM_047440509.1 link	c.-1736_-1729dupCGGAGCCG		5_prime_UTR_variant	Exon 1 of 5		XP_047296465.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAJC5	ENST00000360864 link	c.-51_-44dupCGGAGCCG	5_prime_UTR_variant	Exon 1 of 5	1	NM_025219.3	ENSP00000354111.4	Q9H3Z4-1
DNAJC5	ENST00000470551.1 link	n.-51_-44dupCGGAGCCG	non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000434744.1	Q9H3Z4-2
DNAJC5	ENST00000470551.1 link	n.-51_-44dupCGGAGCCG	5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000434744.1	Q9H3Z4-2
ENSG00000290226	ENST00000703636.1 link	n.453+12464_453+12471dupCGGAGCCG	intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.00977

AC:

1430

AN:

146302

Hom.:

Cov.:

show subpopulations

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:

AN:

870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

Cov.:

AF XY:

0.00930

AC XY:

663

AN XY:

71310

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 05, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over