chr3-132447393-C-G

Position:

• chr3-132447393-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_015268.4(DNAJC13):​c.217C>G​(p.Arg73Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC13 NM_015268.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNAJC13. . Gene score misZ 2.2836 (greater than the threshold 3.09). Trascript score misZ 3.3776 (greater than threshold 3.09). GenCC has associacion of gene with hereditary late onset Parkinson disease.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC13	NM_015268.4	c.217C>G	p.Arg73Gly	missense_variant	4/56	ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2	c.217C>G	p.Arg73Gly	missense_variant	4/57		NP_001316055.1
DNAJC13	XM_047447819.1	c.217C>G	p.Arg73Gly	missense_variant	4/57		XP_047303775.1
DNAJC13	XM_047447820.1	c.217C>G	p.Arg73Gly	missense_variant	4/56		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC13	ENST00000260818.11	c.217C>G	p.Arg73Gly	missense_variant	4/56	1	NM_015268.4	ENSP00000260818	P1
DNAJC13	ENST00000486798.5	n.282C>G		non_coding_transcript_exon_variant	4/20	1
DNAJC13	ENST00000650455.1	c.217C>G	p.Arg73Gly	missense_variant, NMD_transcript_variant	4/57			ENSP00000496825

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.217C>G (p.R73G) alteration is located in exon 4 (coding exon 3) of the DNAJC13 gene. This alteration results from a C to G substitution at nucleotide position 217, causing the arginine (R) at amino acid position 73 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.20
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.011	D
Polyphen		0.65	P
Vest4		0.83
MutPred		0.37		Loss of sheet (P = 0.0126);
MVP		0.36
MPC		0.70
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.61
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-132166237;