chr13-95760146-A-C

Variant summary

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

The NM_006260.5(DNAJC3):ā€‹c.653A>Cā€‹(p.Lys218Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

DNAJC3
NM_006260.5 missense

Scores

2
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70
Variant links:
Genes affected
DNAJC3 (HGNC:9439): (DnaJ heat shock protein family (Hsp40) member C3) This gene encodes a protein with multiple tetratricopeptide repeat (TPR) motifs as well as the highly conserved J domain found in DNAJ chaperone family members. It is a member of the tetratricopeptide repeat family of proteins and acts as an inhibitor of the interferon-induced, dsRNA-activated protein kinase (PKR). [provided by RefSeq, Jul 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAJC3NM_006260.5 linkuse as main transcriptc.653A>C p.Lys218Thr missense_variant 6/12 ENST00000602402.6 NP_006251.1
DNAJC3XM_011521104.3 linkuse as main transcriptc.740A>C p.Lys247Thr missense_variant 7/13 XP_011519406.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAJC3ENST00000602402.6 linkuse as main transcriptc.653A>C p.Lys218Thr missense_variant 6/121 NM_006260.5 ENSP00000473631 P1
DNAJC3ENST00000376795.6 linkuse as main transcriptc.500A>C p.Lys167Thr missense_variant 5/115 ENSP00000365991

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250874
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135576
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460760
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
726682
show subpopulations
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:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152218
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 20, 2022The c.653A>C (p.K218T) alteration is located in exon 6 (coding exon 6) of the DNAJC3 gene. This alteration results from a A to C substitution at nucleotide position 653, causing the lysine (K) at amino acid position 218 to be replaced by a threonine (T). 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
Uncertain
0.39
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T;T
Eigen
Benign
0.076
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.62
D;D
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.4
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.80
T
REVEL
Benign
0.17
Sift4G
Benign
0.59
T;T
Polyphen
0.36
B;.
Vest4
0.83
MutPred
0.38
Loss of ubiquitination at K218 (P = 0.0141);.;
MVP
0.81
MPC
0.90
ClinPred
0.72
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.49
gMVP
0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1033565278; hg19: chr13-96412400; API