20-63895194-TGCCGCCGCCGCC-TGCCGCC

Variant names:

• chr20-63895194-TGCCGCC-T
• rs531246320
• NM_025219.3:c.-125_-120delGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025219.3(DNAJC5):​c.-125_-120delGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 4,518 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAJC5 NM_025219.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000290226 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-125_-120delGCCGCC		5_prime_UTR_variant	Exon 1 of 5	ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-1810_-1805delGCCGCC		5_prime_UTR_variant	Exon 1 of 5		XP_047296465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864	c.-125_-120delGCCGCC		5_prime_UTR_variant	Exon 1 of 5	1	NM_025219.3	ENSP00000354111.4
DNAJC5	ENST00000470551.1	n.-125_-120delGCCGCC		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000434744.1
DNAJC5	ENST00000470551.1	n.-125_-120delGCCGCC		5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000434744.1
ENSG00000290226	ENST00000703636.1	n.453+12390_453+12395delGCCGCC		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149082 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000221 AC: 1 AN: 4518 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000324

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149082 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72632

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;