15-78275648-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001130182.2(DNAJA4):c.797A>C(p.Gln266Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
DNAJA4
NM_001130182.2 missense
NM_001130182.2 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 7.12
Genes affected
DNAJA4 (HGNC:14885): (DnaJ heat shock protein family (Hsp40) member A4) Enables chaperone binding activity and unfolded protein binding activity. Involved in several processes, including negative regulation of endothelial cell migration; negative regulation of inclusion body assembly; and protein refolding. Located in cytosol and membrane. [provided by Alliance of Genome Resources, Apr 2022]
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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 | UniProt |
---|---|---|---|---|---|---|---|
DNAJA4 | NM_001130182.2 | c.797A>C | p.Gln266Pro | missense_variant | 5/7 | ENST00000394852.8 | |
LOC105370910 | XR_932500.3 | n.594-651T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJA4 | ENST00000394852.8 | c.797A>C | p.Gln266Pro | missense_variant | 5/7 | 1 | NM_001130182.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152238Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251418Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135888
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727230
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74384
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 10, 2022 | The c.884A>C (p.Q295P) alteration is located in exon 6 (coding exon 6) of the DNAJA4 gene. This alteration results from a A to C substitution at nucleotide position 884, causing the glutamine (Q) at amino acid position 295 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
T;D;D;T
Sift4G
Benign
T;T;T;T
Polyphen
P;P;P;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at