rs17345563

Positions:

• chr3-132490359-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015268.4(DNAJC13):​c.3469-538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,214 control chromosomes in the GnomAD database, including 809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.093 (809 hom., cov: 32)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC13	NM_015268.4	c.3469-538A>G		intron_variant		ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2	c.3484-538A>G		intron_variant			NP_001316055.1
DNAJC13	XM_047447819.1	c.3484-538A>G		intron_variant			XP_047303775.1
DNAJC13	XM_047447820.1	c.3469-538A>G		intron_variant			XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC13	ENST00000260818.11	c.3469-538A>G		intron_variant		1	NM_015268.4	ENSP00000260818.6
DNAJC13	ENST00000650455.1	n.*1743-538A>G		intron_variant				ENSP00000496825.1

Frequencies

GnomAD3 genomes AF: 0.0926 AC: 14077 AN: 152096 Hom.: 810 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0925 AC: 14082 AN: 152214 Hom.: 809 Cov.: 32 AF XY: 0.0961 AC XY: 7151 AN XY: 74442

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0986 Hom.: 109

Bravo AF: 0.0873

Asia WGS AF: 0.112 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.40

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: rs17345563; hg19: chr3-132209203;