chr3-132446507-C-G

Variant names:

• chr3-132446507-C-G
• NM_015268.4:c.101C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015268.4(DNAJC13):​c.101C>G​(p.Ala34Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAJC13 NM_015268.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.60

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10386658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC13	NM_015268.4	c.101C>G	p.Ala34Gly	missense_variant	Exon 3 of 56	ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2	c.101C>G	p.Ala34Gly	missense_variant	Exon 3 of 57		NP_001316055.1
DNAJC13	XM_047447819.1	c.101C>G	p.Ala34Gly	missense_variant	Exon 3 of 57		XP_047303775.1
DNAJC13	XM_047447820.1	c.101C>G	p.Ala34Gly	missense_variant	Exon 3 of 56		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC13	ENST00000260818.11	c.101C>G	p.Ala34Gly	missense_variant	Exon 3 of 56	1	NM_015268.4	ENSP00000260818.6
DNAJC13	ENST00000486798.5	n.166C>G		non_coding_transcript_exon_variant	Exon 3 of 20	1
DNAJC13	ENST00000650455.1	n.101C>G		non_coding_transcript_exon_variant	Exon 3 of 57			ENSP00000496825.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456482 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724604

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.25
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.44	N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.86	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.31
MutPred		0.40		Loss of sheet (P = 0.0126);
MVP		0.068
MPC		0.24
ClinPred		0.36	T
GERP RS		4.7
Varity_R		0.095
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-132165351;