chr15-40767999-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018163.3(DNAJC17):c.856G>C(p.Glu286Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00119 in 1,605,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E286K) has been classified as Uncertain significance.
Frequency
Consequence
NM_018163.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJC17 | NM_018163.3 | c.856G>C | p.Glu286Gln | missense_variant | 11/11 | ENST00000220496.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJC17 | ENST00000220496.9 | c.856G>C | p.Glu286Gln | missense_variant | 11/11 | 1 | NM_018163.3 | P1 | |
DNAJC17 | ENST00000558727.1 | n.421G>C | non_coding_transcript_exon_variant | 2/2 | 3 | ||||
DNAJC17 | ENST00000561110.5 | n.403G>C | non_coding_transcript_exon_variant | 5/5 | 3 | ||||
DNAJC17 | ENST00000559238.5 | c.*884G>C | 3_prime_UTR_variant, NMD_transcript_variant | 12/12 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000723 AC: 110AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000651 AC: 157AN: 241194Hom.: 0 AF XY: 0.000618 AC XY: 81AN XY: 131050
GnomAD4 exome AF: 0.00124 AC: 1799AN: 1453566Hom.: 0 Cov.: 33 AF XY: 0.00119 AC XY: 862AN XY: 723348
GnomAD4 genome ? AF: 0.000722 AC: 110AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.000644 AC XY: 48AN XY: 74478
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.856G>C (p.E286Q) alteration is located in exon 11 (coding exon 11) of the DNAJC17 gene. This alteration results from a G to C substitution at nucleotide position 856, causing the glutamic acid (E) at amino acid position 286 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 286 of the DNAJC17 protein (p.Glu286Gln). This variant is present in population databases (rs142251536, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DNAJC17-related conditions. ClinVar contains an entry for this variant (Variation ID: 1361751). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at