rs531246320

Variant names:

• chr20-63895194-TGCCGCCGCCGCC-T
• rs531246320
• NM_025219.3:c.-131_-120delGCCGCCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr20-63895194-TGCCGCCGCCGCC-T
• chr20-63895194-TGCCGCCGCCGCC-TGCC
• chr20-63895194-TGCCGCCGCCGCC-TGCCGCC
• chr20-63895194-TGCCGCCGCCGCC-TGCCGCCGCC
• chr20-63895194-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCC
• chr20-63895194-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCC
• chr20-63895194-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCC
• chr20-63895194-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCC
• chr20-63895194-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_025219.3(DNAJC5):​c.-131_-120delGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 153,604 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: DNAJC5 NM_025219.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• ceroid lipofuscinosis, neuronal, 4 (Kufs type)

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• adult neuronal ceroid lipofuscinosis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000290226 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	NM_025219.3	MANE Select	c.-131_-120delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 5	NP_079495.1	Q9H3Z4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC5	ENST00000360864.9	TSL:1 MANE Select	c.-131_-120delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 5	ENSP00000354111.4	Q9H3Z4-1
	DNAJC5	ENST00000898575.1		c.-126_-115delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 5	ENSP00000568634.1
	DNAJC5	ENST00000921989.1		c.-43_-32delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 5	ENSP00000592048.1

Frequencies

GnomAD3 genomes AF: 0.000107 AC: 16 AN: 149082 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000365

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000221 AC: 1 AN: 4522 Hom.: 0 AF XY: 0.000312 AC XY: 1 AN XY: 3202

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 60

American (AMR) AF: 0.00 AC: 0 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 36

East Asian (EAS) AF: 0.00 AC: 0 AN: 202

South Asian (SAS) AF: 0.00 AC: 0 AN: 900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.000323 AC: 1 AN: 3092

Other (OTH) AF: 0.00 AC: 0 AN: 146

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000107 AC: 16 AN: 149082 Hom.: 0 Cov.: 31 AF XY: 0.0000964 AC XY: 7 AN XY: 72632

African (AFR) AF: 0.000365 AC: 15 AN: 41042

American (AMR) AF: 0.00 AC: 0 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66802

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 12

Bravo AF: 0.000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

Other links and lift over

dbSNP: rs531246320; hg19: chr20-62526547;