NM_015268.4:c.68+150A>G

Variant names:

• chr3-132434768-A-G
• rs72990500
• NM_015268.4:c.68+150A>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.68+150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 515,404 control chromosomes in the GnomAD database, including 7,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3102 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4614 hom.)
• Consequence: DNAJC13 NM_015268.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610
• 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=-0.87).
• BP6: Variant 3-132434768-A-G is Benign according to our data. Variant chr3-132434768-A-G is described in ClinVar as Benign. ClinVar VariationId is 1245418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 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.68+150A>G		intron	N/A	NP_056083.3	O75165
	DNAJC13	NM_001329126.2		c.68+150A>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.68+150A>G		intron	N/A	ENSP00000260818.6	O75165
	DNAJC13	ENST00000486798.5	TSL:1	n.133+150A>G		intron	N/A
	DNAJC13	ENST00000650455.1		n.68+150A>G		intron	N/A	ENSP00000496825.1	A0A3B3IRM0

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29717 AN: 152048 Hom.: 3098 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.147 AC: 53457 AN: 363238 Hom.: 4614 AF XY: 0.148 AC XY: 27651 AN XY: 187150

African (AFR) AF: 0.248 AC: 2416 AN: 9728

American (AMR) AF: 0.173 AC: 2087 AN: 12074

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 1701 AN: 10514

East Asian (EAS) AF: 0.160 AC: 4040 AN: 25234

South Asian (SAS) AF: 0.160 AC: 3090 AN: 19348

European-Finnish (FIN) AF: 0.171 AC: 3743 AN: 21906

Middle Eastern (MID) AF: 0.181 AC: 278 AN: 1536

European-Non Finnish (NFE) AF: 0.136 AC: 33042 AN: 242708

Other (OTH) AF: 0.152 AC: 3060 AN: 20190

GnomAD4 genome AF: 0.195 AC: 29733 AN: 152166 Hom.: 3102 Cov.: 32 AF XY: 0.196 AC XY: 14591 AN XY: 74400

African (AFR) AF: 0.269 AC: 11182 AN: 41508

American (AMR) AF: 0.187 AC: 2858 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3472

East Asian (EAS) AF: 0.158 AC: 821 AN: 5182

South Asian (SAS) AF: 0.176 AC: 848 AN: 4822

European-Finnish (FIN) AF: 0.206 AC: 2174 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10646 AN: 68002

Other (OTH) AF: 0.188 AC: 396 AN: 2110

Alfa AF: 0.174 Hom.: 296

Bravo AF: 0.197

Asia WGS AF: 0.167 AC: 584 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	-0.87
CADD	Benign	1.8
DANN	Benign	0.36
PhyloP100		-0.061
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: rs72990500; hg19: chr3-132153612;