21-33488366-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040192.3(DNAJC28):​c.1028C>A​(p.Thr343Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T343I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNAJC28
NM_001040192.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

0 publications found
Variant links:
Genes affected
DNAJC28 (HGNC:1297): (DnaJ heat shock protein family (Hsp40) member C28) This gene encodes a member of the DnaJ heat shock protein family. The encoded protein, which contains a conserved N-terminal DnaJ domain, is thought to play a role in protein folding or act as a molecular chaperone protein. [provided by RefSeq, Oct 2016]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07765657).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAJC28NM_001040192.3 linkc.1028C>A p.Thr343Asn missense_variant Exon 2 of 2 ENST00000381947.4 NP_001035282.1 Q9NX36
DNAJC28NM_001320746.3 linkc.1028C>A p.Thr343Asn missense_variant Exon 2 of 2 NP_001307675.1 Q9NX36
DNAJC28NM_017833.5 linkc.1028C>A p.Thr343Asn missense_variant Exon 2 of 2 NP_060303.2 Q9NX36

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAJC28ENST00000381947.4 linkc.1028C>A p.Thr343Asn missense_variant Exon 2 of 2 1 NM_001040192.3 ENSP00000371373.3 Q9NX36
DNAJC28ENST00000314399.3 linkc.1028C>A p.Thr343Asn missense_variant Exon 2 of 2 1 ENSP00000320303.3 Q9NX36
DNAJC28ENST00000402202.1 linkc.1028C>A p.Thr343Asn missense_variant Exon 2 of 2 5 ENSP00000385777.1 Q9NX36

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000432
AC:
1
AN:
231744
AF XY:
0.00
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000919
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.94e-7
AC:
1
AN:
1440090
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
715842
show subpopulations
African (AFR)
AF:
0.0000314
AC:
1
AN:
31804
American (AMR)
AF:
0.00
AC:
0
AN:
37874
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25278
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39502
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53112
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5672
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1106618
Other (OTH)
AF:
0.00
AC:
0
AN:
59400
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
13
DANN
Benign
0.62
DEOGEN2
Benign
0.0023
T;T;T;T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.40
N
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.078
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
M;M;M;M
PhyloP100
1.8
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.10
.;N;N;N
REVEL
Benign
0.099
Sift
Benign
0.079
.;T;T;T
Sift4G
Benign
0.53
T;T;T;T
Polyphen
0.013
B;B;B;B
Vest4
0.067
MutPred
0.32
Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);
MVP
0.21
MPC
0.036
ClinPred
0.042
T
GERP RS
4.3
Varity_R
0.065
gMVP
0.23
Mutation Taster
=93/7
polymorphism

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

Other links and lift over

dbSNP: rs776588830; hg19: chr21-34860673; API