rs387907571

Variant names:

• chr3-132477995-A-C
• NM_015268.4:c.2564A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-132477995-A-C
• chr3-132477995-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015268.4(DNAJC13):​c.2564A>C​(p.Asn855Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 8.71

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
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC13	NM_015268.4	c.2564A>C	p.Asn855Thr	missense_variant	Exon 24 of 56	ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2	c.2579A>C	p.Asn860Thr	missense_variant	Exon 25 of 57		NP_001316055.1
DNAJC13	XM_047447819.1	c.2579A>C	p.Asn860Thr	missense_variant	Exon 25 of 57		XP_047303775.1
DNAJC13	XM_047447820.1	c.2564A>C	p.Asn855Thr	missense_variant	Exon 24 of 56		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC13	ENST00000260818.11	c.2564A>C	p.Asn855Thr	missense_variant	Exon 24 of 56	1	NM_015268.4	ENSP00000260818.6
DNAJC13	ENST00000464766.1	n.401A>C		non_coding_transcript_exon_variant	Exon 4 of 7	5
DNAJC13	ENST00000650455.1	n.*712A>C		non_coding_transcript_exon_variant	Exon 24 of 57			ENSP00000496825.1
DNAJC13	ENST00000650455.1	n.*712A>C		3_prime_UTR_variant	Exon 24 of 57			ENSP00000496825.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449748 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 720684

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Uncertain	0.55
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.84
MutPred		0.55		Gain of glycosylation at S850 (P = 0.0496);
MVP		0.26
MPC		0.71
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.57

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: chr3-132196839;