rs144868266

Variant names:

• chr3-132434331-AGCAAAGATCGTGC-A
• rs144868266
• NM_015268.4:c.-13-206_-13-194delGCAAAGATCGTGC

Variant summary

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

The NM_015268.4(DNAJC13):​c.-13-206_-13-194delGCAAAGATCGTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 151,442 control chromosomes in the GnomAD database, including 487 homozygotes. 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. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.046 (487 hom., cov: 29)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.560
• 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 3-132434331-AGCAAAGATCGTGC-A is Benign according to our data. Variant chr3-132434331-AGCAAAGATCGTGC-A is described in ClinVar as Benign. ClinVar VariationId is 1230766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 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.-13-206_-13-194delGCAAAGATCGTGC		intron	N/A	NP_056083.3	O75165
	DNAJC13	NM_001329126.2		c.-13-206_-13-194delGCAAAGATCGTGC		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.-13-206_-13-194delGCAAAGATCGTGC		intron	N/A	ENSP00000260818.6	O75165
	DNAJC13	ENST00000486798.5	TSL:1	n.53-206_53-194delGCAAAGATCGTGC		intron	N/A
	DNAJC13	ENST00000650455.1		n.-13-206_-13-194delGCAAAGATCGTGC		intron	N/A	ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6927 AN: 151338 Hom.: 486 Cov.: 29

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00102

Gnomad OTH AF: 0.0371

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

GnomAD4 genome AF: 0.0458 AC: 6938 AN: 151442 Hom.: 487 Cov.: 29 AF XY: 0.0436 AC XY: 3232 AN XY: 74060

African (AFR) AF: 0.153 AC: 6294 AN: 41086

American (AMR) AF: 0.0200 AC: 305 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3468

East Asian (EAS) AF: 0.0295 AC: 152 AN: 5144

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10488

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00102 AC: 69 AN: 67906

Other (OTH) AF: 0.0371 AC: 78 AN: 2100

Alfa AF: 0.0441 Hom.: 37

Asia WGS AF: 0.0230 AC: 80 AN: 3476

ClinVar

ClinVar submissions

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		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs144868266; hg19: chr3-132153175;