3-132434209-CAAAAAAA-CAAAAAA

Variant names:

• chr3-132434209-CA-C
• rs544393571
• NM_015268.4:c.-13-317delA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015268.4(DNAJC13):​c.-13-317delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 107,388 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00045 (0 hom., cov: 26)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 0 publications found

Genes affected

DNAJC13 (HGNC:30343): (DnaJ heat shock protein family (Hsp40) member C13) This gene encodes a member of the Dnaj protein family whose members act as co-chaperones of a partner heat-shock protein by binding to the latter and stimulating ATP hydrolysis. The encoded protein associates with the heat-shock protein Hsc70 and plays a role in clathrin-mediated endocytosis. It may also be involved in post-endocytic transport mechanisms via its associations with other proteins, including the sorting nexin SNX1. Mutations in this gene are associated with Parkinson's disease. [provided by RefSeq, Jun 2016]

DNAJC13 Gene-Disease associations (from GenCC):

• hereditary late onset Parkinson disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015268.4. 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
	DNAJC13	NM_015268.4	MANE Select	c.-13-317delA		intron	N/A	NP_056083.3	O75165
	DNAJC13	NM_001329126.2		c.-13-317delA		intron	N/A	NP_001316055.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC13	ENST00000260818.11	TSL:1 MANE Select	c.-13-328delA		intron	N/A	ENSP00000260818.6	O75165
	DNAJC13	ENST00000486798.5	TSL:1	n.53-328delA		intron	N/A
	DNAJC13	ENST00000650455.1		n.-13-328delA		intron	N/A	ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 48 AN: 107388 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000306

Gnomad ASJ AF: 0.000348

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00187

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000490

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000447 AC: 48 AN: 107388 Hom.: 0 Cov.: 26 AF XY: 0.000376 AC XY: 19 AN XY: 50514

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

African (AFR) AF: 0.000330 AC: 9 AN: 27278

American (AMR) AF: 0.000306 AC: 3 AN: 9800

Ashkenazi Jewish (ASJ) AF: 0.000348 AC: 1 AN: 2874

East Asian (EAS) AF: 0.00 AC: 0 AN: 3862

South Asian (SAS) AF: 0.00 AC: 0 AN: 3418

European-Finnish (FIN) AF: 0.00187 AC: 9 AN: 4810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 192

European-Non Finnish (NFE) AF: 0.000490 AC: 26 AN: 53082

Other (OTH) AF: 0.00 AC: 0 AN: 1412

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000135976), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000726 Hom.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs544393571; hg19: chr3-132153053;