rs2369796

chr3-132477972-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015268.4(DNAJC13):c.2550-9A>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003163
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.0150

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1210029.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-132477972-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC13	NM_015268.4	c.2550-9A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000260818.11
DNAJC13	NM_001329126.2	c.2565-9A>T		splice_polypyrimidine_tract_variant, intron_variant
DNAJC13	XM_047447819.1	c.2565-9A>T		splice_polypyrimidine_tract_variant, intron_variant
DNAJC13	XM_047447820.1	c.2550-9A>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC13	ENST00000260818.11	c.2550-9A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015268.4	P1
DNAJC13	ENST00000650455.1	c.*698-9A>T		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant
DNAJC13	ENST00000464766.1	n.387-9A>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.481 AC: 100248 AN: 208392 Hom.: 21004 AF XY: 0.473 AC XY: 53555 AN XY: 113196

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 SAS exome AF: 0.521

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

Gnomad4 AFR exome AF: 0.832

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.826

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.453

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.491

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

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.571

Alfa AF: 0.513 Hom.: 5120

Bravo AF: 0.634

Asia WGS AF: 0.743 AC: 2578 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.010
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2369796; hg19: chr3-132196816;