3-132535246-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	UniProt
DNAJC13	NM_015268.4	c.6626-2930A>T		intron_variant		ENST00000260818.11
DNAJC13	NM_001329126.2	c.6641-2930A>T		intron_variant
DNAJC13	XM_047447819.1	c.6641-2930A>T		intron_variant
DNAJC13	XM_047447820.1	c.6626-2930A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC13	ENST00000260818.11	c.6626-2930A>T		intron_variant		1	NM_015268.4	P1
DNAJC13	ENST00000509279.1	c.232-1912A>T		intron_variant, NMD_transcript_variant		5
DNAJC13	ENST00000650455.1	c.*4900-2930A>T		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.548

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

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: rs1378810; hg19: chr3-132254090;