20-63895308-GCGGGCGGA-G

Position:

• chr20-63895308-GCGGGCGGA-G

Variant summary

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

The NM_025219.3(DNAJC5):​c.-21_-14delGGACGGGC variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 147,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.00018 (0 hom., cov: 32)
• Consequence: DNAJC5 NM_025219.3 splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.20

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]

ENSG00000290226 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 20-63895308-GCGGGCGGA-G is Benign according to our data. Variant chr20-63895308-GCGGGCGGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 420557.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-21_-14delGGACGGGC		splice_region_variant	1/5	ENST00000360864.9	NP_079495.1
DNAJC5	NM_025219.3	c.-21_-14delGGACGGGC		5_prime_UTR_variant	1/5	ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-1706_-1699delGGACGGGC		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.-21_-14delGGACGGGC		splice_region_variant	1/5	1	NM_025219.3	ENSP00000354111.4
DNAJC5	ENST00000360864.9	c.-21_-14delGGACGGGC		5_prime_UTR_variant	1/5	1	NM_025219.3	ENSP00000354111.4

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 27 AN: 146990 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000676

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000455

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000184 AC: 27 AN: 147082 Hom.: 0 Cov.: 32 AF XY: 0.000195 AC XY: 14 AN XY: 71622

Gnomad4 AFR AF: 0.000536

Gnomad4 AMR AF: 0.0000675

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000455

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000170

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

Mar 09, 2016

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: rs1064794557; hg19: chr20-62526661;