3-132477972-A-T

Variant names:

• chr3-132477972-A-T
• rs2369796
• NM_015268.4:c.2550-9A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015268.4(DNAJC13):​c.2550-9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,551,476 control chromosomes in the GnomAD database, including 170,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (31126 hom., cov: 29)
  • Exomes 𝑓: 0.47 (139471 hom.)
• Consequence: DNAJC13 NM_015268.4 intron
• Scores: Splicing: ADA: 0.00003163
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0150
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-132477972-A-T is Benign according to our data. Variant chr3-132477972-A-T is described in ClinVar as Benign. ClinVar VariationId is 1210029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC13	NM_015268.4	MANE Select	c.2550-9A>T		intron	N/A	NP_056083.3
	DNAJC13	NM_001329126.2		c.2565-9A>T		intron	N/A	NP_001316055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC13	ENST00000260818.11	TSL:1 MANE Select	c.2550-9A>T		intron	N/A	ENSP00000260818.6
	DNAJC13	ENST00000464766.1	TSL:5	n.387-9A>T		intron	N/A
	DNAJC13	ENST00000650455.1		n.*698-9A>T		intron	N/A	ENSP00000496825.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 92339 AN: 150374 Hom.: 31068 Cov.: 29

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.567

GnomAD2 exomes AF: 0.481 AC: 100248 AN: 208392 AF XY: 0.473

Gnomad AFR exome AF: 0.817

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.786

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.444

GnomAD4 exome AF: 0.466 AC: 653314 AN: 1400998 Hom.: 139471 Cov.: 35 AF XY: 0.468 AC XY: 325580 AN XY: 696168

African (AFR) AF: 0.832 AC: 24288 AN: 29180

American (AMR) AF: 0.475 AC: 17664 AN: 37202

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11081 AN: 24434

East Asian (EAS) AF: 0.826 AC: 30231 AN: 36588

South Asian (SAS) AF: 0.561 AC: 43603 AN: 77784

European-Finnish (FIN) AF: 0.453 AC: 23287 AN: 51456

Middle Eastern (MID) AF: 0.470 AC: 2589 AN: 5510

European-Non Finnish (NFE) AF: 0.437 AC: 472332 AN: 1081314

Other (OTH) AF: 0.491 AC: 28239 AN: 57530

GnomAD4 genome AF: 0.614 AC: 92452 AN: 150478 Hom.: 31126 Cov.: 29 AF XY: 0.615 AC XY: 45173 AN XY: 73460

African (AFR) AF: 0.897 AC: 36691 AN: 40912

American (AMR) AF: 0.533 AC: 8063 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1692 AN: 3462

East Asian (EAS) AF: 0.901 AC: 4575 AN: 5080

South Asian (SAS) AF: 0.642 AC: 3044 AN: 4744

European-Finnish (FIN) AF: 0.469 AC: 4818 AN: 10282

Middle Eastern (MID) AF: 0.490 AC: 141 AN: 288

European-Non Finnish (NFE) AF: 0.473 AC: 31929 AN: 67568

Other (OTH) AF: 0.571 AC: 1194 AN: 2092

Alfa AF: 0.513 Hom.: 5120

Bravo AF: 0.634

Asia WGS AF: 0.743 AC: 2578 AN: 3468

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.010
DANN	Benign	0.74
PhyloP100		0.015
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0040
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: rs2369796; hg19: chr3-132196816;