3-132434209-C-CA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015268.4(DNAJC13):​c.-13-317dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 107,208 control chromosomes in the GnomAD database, including 942 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (942 hom., cov: 26)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-132434209-C-CA is Benign according to our data. Variant chr3-132434209-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1286197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

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.-13-317dupA		intron	N/A	NP_056083.3	O75165
	DNAJC13	NM_001329126.2		c.-13-317dupA		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.-13-329_-13-328insA		intron	N/A	ENSP00000260818.6	O75165
	DNAJC13	ENST00000486798.5	TSL:1	n.53-329_53-328insA		intron	N/A
	DNAJC13	ENST00000650455.1		n.-13-329_-13-328insA		intron	N/A	ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes AF: 0.133 AC: 14273 AN: 107172 Hom.: 943 Cov.: 26

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.133 AC: 14266 AN: 107208 Hom.: 942 Cov.: 26 AF XY: 0.137 AC XY: 6912 AN XY: 50458

African (AFR) AF: 0.0366 AC: 999 AN: 27300

American (AMR) AF: 0.177 AC: 1728 AN: 9774

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 527 AN: 2876

East Asian (EAS) AF: 0.149 AC: 575 AN: 3850

South Asian (SAS) AF: 0.194 AC: 658 AN: 3388

European-Finnish (FIN) AF: 0.223 AC: 1070 AN: 4798

Middle Eastern (MID) AF: 0.178 AC: 32 AN: 180

European-Non Finnish (NFE) AF: 0.158 AC: 8382 AN: 52964

Other (OTH) AF: 0.136 AC: 193 AN: 1418

Alfa AF: 0.0226 Hom.: 30

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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;