1-28232967-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014280.3(DNAJC8):​c.32G>A​(p.Gly11Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,184 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000069 ( 1 hom. )

Consequence

DNAJC8
NM_014280.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.186
Variant links:
Genes affected
DNAJC8 (HGNC:15470): (DnaJ heat shock protein family (Hsp40) member C8) Enables Hsp70 protein binding activity. Located in cytosol; intercellular bridge; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.17143935).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAJC8NM_014280.3 linkc.32G>A p.Gly11Asp missense_variant Exon 1 of 9 ENST00000263697.6 NP_055095.2 O75937
DNAJC8NR_159454.1 linkn.63G>A non_coding_transcript_exon_variant Exon 1 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAJC8ENST00000263697.6 linkc.32G>A p.Gly11Asp missense_variant Exon 1 of 9 1 NM_014280.3 ENSP00000263697.4 O75937
DNAJC8ENST00000489277.5 linkn.59G>A non_coding_transcript_exon_variant Exon 1 of 10 1 ENSP00000518780.1
DNAJC8ENST00000482674.5 linkn.38G>A non_coding_transcript_exon_variant Exon 1 of 4 2
DNAJC8ENST00000488868.1 linkn.54G>A non_coding_transcript_exon_variant Exon 1 of 5 4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152158
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
248726
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135042
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000334
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000691
AC:
101
AN:
1460908
Hom.:
1
Cov.:
31
AF XY:
0.0000688
AC XY:
50
AN XY:
726848
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00247
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152276
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000331
AC:
4
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 specified Uncertain:1
Feb 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.32G>A (p.G11D) alteration is located in exon 1 (coding exon 1) of the DNAJC8 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the glycine (G) at amino acid position 11 to be replaced by an aspartic acid (D). 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
Benign
0.18
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.013
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.40
FATHMM_MKL
Uncertain
0.87
D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
0.12
N
REVEL
Benign
0.17
Sift
Benign
0.44
T
Sift4G
Benign
0.33
T
Polyphen
0.87
P
Vest4
0.55
MVP
0.71
MPC
1.0
ClinPred
0.16
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.068
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs199527099; hg19: chr1-28559478; API