3-132446211-T-A

Variant names:

• chr3-132446211-T-A
• rs1979847
• NM_015268.4:c.69-264T>A

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.69-264T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,600 control chromosomes in the GnomAD database, including 20,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (20230 hom., cov: 31)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• Publications: 1 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=-0.84).
• BP6: Variant 3-132446211-T-A is Benign according to our data. Variant chr3-132446211-T-A is described in ClinVar as Benign. ClinVar VariationId is 1263992.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 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.69-264T>A		intron	N/A	NP_056083.3	O75165
	DNAJC13	NM_001329126.2		c.69-264T>A		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.69-264T>A		intron	N/A	ENSP00000260818.6	O75165
	DNAJC13	ENST00000486798.5	TSL:1	n.134-264T>A		intron	N/A
	DNAJC13	ENST00000650455.1		n.69-264T>A		intron	N/A	ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75896 AN: 151484 Hom.: 20187 Cov.: 31

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.501 AC: 75983 AN: 151600 Hom.: 20230 Cov.: 31 AF XY: 0.507 AC XY: 37508 AN XY: 74036

African (AFR) AF: 0.647 AC: 26763 AN: 41392

American (AMR) AF: 0.472 AC: 7180 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1306 AN: 3464

East Asian (EAS) AF: 0.835 AC: 4322 AN: 5178

South Asian (SAS) AF: 0.582 AC: 2804 AN: 4814

European-Finnish (FIN) AF: 0.428 AC: 4464 AN: 10438

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27733 AN: 67780

Other (OTH) AF: 0.454 AC: 958 AN: 2108

Alfa AF: 0.271 Hom.: 562

Bravo AF: 0.510

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	-0.84
CADD	Benign	0.44
DANN	Benign	0.30
PhyloP100		-1.1
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: rs1979847; hg19: chr3-132165055;