NM_015268.4:c.-13-249C>G

Variant names:

• chr3-132434289-C-G
• rs9864899
• NM_015268.4:c.-13-249C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015268.4(DNAJC13):​c.-13-249C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 140,476 control chromosomes in the GnomAD database, including 67,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.98 (67594 hom., cov: 27)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.840
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 3-132434289-C-G is Benign according to our data. Variant chr3-132434289-C-G is described in ClinVar as Benign. ClinVar VariationId is 1265563.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015268.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC13	NM_015268.4	MANE Select	c.-13-249C>G		intron	N/A	NP_056083.3	O75165
	DNAJC13	NM_001329126.2		c.-13-249C>G		intron	N/A	NP_001316055.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC13	ENST00000260818.11	TSL:1 MANE Select	c.-13-249C>G		intron	N/A	ENSP00000260818.6	O75165
	DNAJC13	ENST00000486798.5	TSL:1	n.53-249C>G		intron	N/A
	DNAJC13	ENST00000650455.1		n.-13-249C>G		intron	N/A	ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes AF: 0.981 AC: 137709 AN: 140382 Hom.: 67550 Cov.: 27

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.992

Gnomad MID AF: 0.986

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.987

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

GnomAD4 genome AF: 0.981 AC: 137800 AN: 140476 Hom.: 67594 Cov.: 27 AF XY: 0.981 AC XY: 67496 AN XY: 68796

African (AFR) AF: 0.985 AC: 37502 AN: 38058

American (AMR) AF: 0.938 AC: 13569 AN: 14462

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3168 AN: 3212

East Asian (EAS) AF: 0.990 AC: 4788 AN: 4838

South Asian (SAS) AF: 0.987 AC: 4428 AN: 4486

European-Finnish (FIN) AF: 0.992 AC: 9644 AN: 9724

Middle Eastern (MID) AF: 0.981 AC: 255 AN: 260

European-Non Finnish (NFE) AF: 0.985 AC: 61673 AN: 62628

Other (OTH) AF: 0.988 AC: 1964 AN: 1988

Alfa AF: 0.994 Hom.: 9140

Bravo AF: 0.991

Asia WGS AF: 0.986 AC: 3428 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.98
DANN	Benign	0.25
PhyloP100		-0.84
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: rs9864899; hg19: chr3-132153133;