chr5-55270451-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_019030.4(DHX29):c.3030C>G(p.Ile1010Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
DHX29
NM_019030.4 missense
NM_019030.4 missense
Scores
3
3
13
Clinical Significance
Conservation
PhyloP100: -0.0330
Genes affected
DHX29 (HGNC:15815): (DExH-box helicase 29) This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helicases. The encoded protein functions in translation initiation, and is specifically required for ribosomal scanning across stable mRNA secondary structures during initiation codon selection. This protein may also play a role in sensing virally derived cytosolic nucleic acids. Knockdown of this gene results in reduced protein translation and impaired proliferation of cancer cells. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.844
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHX29 | NM_019030.4 | c.3030C>G | p.Ile1010Met | missense_variant | 20/27 | ENST00000251636.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHX29 | ENST00000251636.10 | c.3030C>G | p.Ile1010Met | missense_variant | 20/27 | 1 | NM_019030.4 | P1 | |
DHX29 | ENST00000504778.5 | n.3238C>G | non_coding_transcript_exon_variant | 20/27 | 1 | ||||
CCNO-DT | ENST00000506435.1 | n.108-9082G>C | intron_variant, non_coding_transcript_variant | 3 | |||||
DHX29 | ENST00000513447.1 | n.837C>G | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249522Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134922
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GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460502Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726530
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GnomAD4 genome ? Cov.: 32
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?
Cov.:
32
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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 | Jun 02, 2023 | The c.3030C>G (p.I1010M) alteration is located in exon 20 (coding exon 20) of the DHX29 gene. This alteration results from a C to G substitution at nucleotide position 3030, causing the isoleucine (I) at amino acid position 1010 to be replaced by a methionine (M). 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
Uncertain
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Pathogenic
D;D
Polyphen
P;.
Vest4
MutPred
Loss of catalytic residue at I1010 (P = 0.0088);Loss of catalytic residue at I1010 (P = 0.0088);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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