rs1057519436
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_138615.3(DHX30):c.1478G>A(p.Arg493His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
DHX30
NM_138615.3 missense
NM_138615.3 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 9.91
Genes affected
DHX30 (HGNC:16716): (DExH-box helicase 30) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The family member encoded by this gene is a mitochondrial nucleoid protein that associates with mitochondrial DNA. It has also been identified as a component of a transcriptional repressor complex that functions in retinal development, and it is required to optimize the function of the zinc-finger antiviral protein. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
In a domain Helicase ATP-binding (size 168) in uniprot entity DHX30_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_138615.3
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DHX30. . Gene score misZ 5.2961 (greater than the threshold 3.09). Trascript score misZ 6.8999 (greater than threshold 3.09). GenCC has associacion of gene with neurodevelopmental disorder with severe motor impairment and absent language.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.975
PP5
Variant 3-47846550-G-A is Pathogenic according to our data. Variant chr3-47846550-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 375374.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-47846550-G-A is described in Lovd as [Pathogenic]. Variant chr3-47846550-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DHX30 | NM_138615.3 | c.1478G>A | p.Arg493His | missense_variant | 11/22 | ENST00000445061.6 | NP_619520.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DHX30 | ENST00000445061.6 | c.1478G>A | p.Arg493His | missense_variant | 11/22 | 1 | NM_138615.3 | ENSP00000405620.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neurodevelopmental disorder with severe motor impairment and absent language Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 27, 2023 | - - |
not provided Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Seizure;C0038379:Strabismus;C0231686:Unsteady gait;C0349588:Short stature;C3489733:Oculomotor apraxia;C4551563:Microcephaly Pathogenic:1
Pathogenic, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | This variant was identified as de novo in an individual with seizures, microcephaly, short stature, strabismus, oculomotor apraxia, unsteady gait. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
T;T;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
.;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;.;H;.;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;.;D
REVEL
Uncertain
Sift
Pathogenic
D;D;.;.;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;.;D;D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0205);.;Loss of MoRF binding (P = 0.0205);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at