3-132490359-A-G

Variant names:

• chr3-132490359-A-G
• rs17345563
• NM_015268.4:c.3469-538A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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 -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 rank	MANE	Protein	UniProt
DNAJC13	NM_015268.4	c.3469-538A>G		intron_variant	Intron 31 of 55	ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2	c.3484-538A>G		intron_variant	Intron 32 of 56		NP_001316055.1
DNAJC13	XM_047447819.1	c.3484-538A>G		intron_variant	Intron 32 of 56		XP_047303775.1
DNAJC13	XM_047447820.1	c.3469-538A>G		intron_variant	Intron 31 of 55		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC13	ENST00000260818.11	c.3469-538A>G		intron_variant	Intron 31 of 55	1	NM_015268.4	ENSP00000260818.6
DNAJC13	ENST00000650455.1	n.*1743-538A>G		intron_variant	Intron 32 of 56			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

African (AFR) AF: 0.0231 AC: 958 AN: 41554

American (AMR) AF: 0.123 AC: 1877 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3470

East Asian (EAS) AF: 0.102 AC: 531 AN: 5182

South Asian (SAS) AF: 0.138 AC: 665 AN: 4824

European-Finnish (FIN) AF: 0.144 AC: 1531 AN: 10604

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7751 AN: 67978

Other (OTH) AF: 0.104 AC: 220 AN: 2110

Alfa AF: 0.0961 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
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17345563; hg19: chr3-132209203;