1-28201357-C-T

Variant summary

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

The NM_014280.3(DNAJC8):​c.653G>A​(p.Gly218Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

DNAJC8
NM_014280.3 missense

Scores

5
6
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56
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 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAJC8NM_014280.3 linkc.653G>A p.Gly218Asp missense_variant Exon 9 of 9 ENST00000263697.6 NP_055095.2 O75937
DNAJC8NR_159454.1 linkn.806G>A non_coding_transcript_exon_variant Exon 10 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAJC8ENST00000263697.6 linkc.653G>A p.Gly218Asp missense_variant Exon 9 of 9 1 NM_014280.3 ENSP00000263697.4 O75937
DNAJC8ENST00000489277.5 linkn.802G>A non_coding_transcript_exon_variant Exon 10 of 10 1 ENSP00000518780.1
DNAJC8ENST00000603289.5 linkc.182G>A p.Gly61Asp missense_variant Exon 3 of 5 5 ENSP00000474440.2 S4R3J5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.653G>A (p.G218D) alteration is located in exon 9 (coding exon 9) of the DNAJC8 gene. This alteration results from a G to A substitution at nucleotide position 653, causing the glycine (G) at amino acid position 218 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
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0066
T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.052
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.31
N
REVEL
Uncertain
0.30
Sift
Benign
0.26
T
Sift4G
Benign
0.53
T
Polyphen
0.82
P
Vest4
0.84
MutPred
0.14
Loss of MoRF binding (P = 0.0644);
MVP
0.85
MPC
1.1
ClinPred
0.81
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.34
gMVP
0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-28527868; API