3-132535246-A-T

Variant names:

• chr3-132535246-A-T
• rs1378810
• NM_015268.4:c.6626-2930A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015268.4(DNAJC13):​c.6626-2930A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,164 control chromosomes in the GnomAD database, including 28,467 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 0.59 (28467 hom., cov: 33)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC13	NM_015268.4	c.6626-2930A>T		intron_variant	Intron 55 of 55	ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2	c.6641-2930A>T		intron_variant	Intron 56 of 56		NP_001316055.1
DNAJC13	XM_047447819.1	c.6641-2930A>T		intron_variant	Intron 56 of 56		XP_047303775.1
DNAJC13	XM_047447820.1	c.6626-2930A>T		intron_variant	Intron 55 of 55		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC13	ENST00000260818.11	c.6626-2930A>T		intron_variant	Intron 55 of 55	1	NM_015268.4	ENSP00000260818.6
DNAJC13	ENST00000509279.1	n.230-1912A>T		intron_variant	Intron 2 of 3	5		ENSP00000426240.1
DNAJC13	ENST00000650455.1	n.*4900-2930A>T		intron_variant	Intron 56 of 56			ENSP00000496825.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89244 AN: 152046 Hom.: 28418 Cov.: 33

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.587 AC: 89353 AN: 152164 Hom.: 28467 Cov.: 33 AF XY: 0.589 AC XY: 43802 AN XY: 74406

African (AFR) AF: 0.832 AC: 34561 AN: 41530

American (AMR) AF: 0.511 AC: 7807 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1642 AN: 3468

East Asian (EAS) AF: 0.868 AC: 4499 AN: 5182

South Asian (SAS) AF: 0.638 AC: 3071 AN: 4810

European-Finnish (FIN) AF: 0.471 AC: 4987 AN: 10594

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31206 AN: 67986

Other (OTH) AF: 0.548 AC: 1157 AN: 2112

Alfa AF: 0.526 Hom.: 2771

Bravo AF: 0.600

Asia WGS AF: 0.756 AC: 2630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.10
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: rs1378810; hg19: chr3-132254090;