rs10512859

chr3-132488524-T-C

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.3422+72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 1,372,190 control chromosomes in the GnomAD database, including 1,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (482 hom., cov: 32)
  • Exomes 𝑓: 0.021 (590 hom.)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.157

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=-0.82).
• BP6: Variant 3-132488524-T-C is Benign according to our data. Variant chr3-132488524-T-C is described in ClinVar as [Benign]. Clinvar id is 1289826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC13	NM_015268.4	c.3422+72T>C		intron_variant		ENST00000260818.11
DNAJC13	NM_001329126.2	c.3437+72T>C		intron_variant
DNAJC13	XM_047447819.1	c.3437+72T>C		intron_variant
DNAJC13	XM_047447820.1	c.3422+72T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC13	ENST00000260818.11	c.3422+72T>C		intron_variant		1	NM_015268.4	P1
DNAJC13	ENST00000650455.1	c.*1696+72T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8356 AN: 152112 Hom.: 481 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0426

GnomAD4 exome AF: 0.0215 AC: 26201 AN: 1219960 Hom.: 590 AF XY: 0.0209 AC XY: 12639 AN XY: 605064

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0163

Gnomad4 ASJ exome AF: 0.0129

Gnomad4 EAS exome AF: 0.000108

Gnomad4 SAS exome AF: 0.00555

Gnomad4 FIN exome AF: 0.0337

Gnomad4 NFE exome AF: 0.0191

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0550 AC: 8369 AN: 152230 Hom.: 482 Cov.: 32 AF XY: 0.0534 AC XY: 3975 AN XY: 74432

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0343

Gnomad4 NFE AF: 0.0200

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0362 Hom.: 52

Bravo AF: 0.0583

Asia WGS AF: 0.0110 AC: 38 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.4
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs10512859; hg19: chr3-132207368;