13-95760064-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBS1_Supporting

The NM_006260.5(DNAJC3):​c.571C>T​(p.Arg191Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,604,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

DNAJC3
NM_006260.5 missense

Scores

6
10
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.848
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00000826 (12/1452480) while in subpopulation MID AF= 0.000701 (4/5710). AF 95% confidence interval is 0.000239. There are 0 homozygotes in gnomad4_exome. There are 6 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAJC3NM_006260.5 linkuse as main transcriptc.571C>T p.Arg191Trp missense_variant 6/12 ENST00000602402.6 NP_006251.1 Q13217A8KA82
DNAJC3XM_011521104.3 linkuse as main transcriptc.658C>T p.Arg220Trp 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.571C>T p.Arg191Trp missense_variant 6/121 NM_006260.5 ENSP00000473631.1 Q13217
DNAJC3ENST00000376795.6 linkuse as main transcriptc.418C>T p.Arg140Trp missense_variant 5/115 ENSP00000365991.6 X6R9L0

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152146
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:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248082
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
134206
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000298
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:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000826
AC:
12
AN:
1452480
Hom.:
0
Cov.:
30
AF XY:
0.00000830
AC XY:
6
AN XY:
722552
show subpopulations
Gnomad4 AFR exome
AF:
0.0000603
Gnomad4 AMR exome
AF:
0.0000229
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000361
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152264
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74444
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:
0.00
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingMayo Clinic Laboratories, Mayo ClinicSep 23, 2024PM2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.66
D;T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Uncertain
0.30
D
MutationAssessor
Pathogenic
3.3
M;.
PrimateAI
Uncertain
0.74
T
REVEL
Uncertain
0.56
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;.
Vest4
0.86
MVP
0.89
MPC
1.2
ClinPred
0.99
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.72
gMVP
0.78

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: rs372983173; hg19: chr13-96412318; API