17-5450285-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020162.4(DHX33):c.1646G>A(p.Arg549His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R549C) has been classified as Uncertain significance.
Frequency
Consequence
NM_020162.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DHX33 | NM_020162.4 | c.1646G>A | p.Arg549His | missense_variant | Exon 10 of 12 | ENST00000225296.8 | NP_064547.2 | |
DHX33 | NM_001199699.2 | c.1127G>A | p.Arg376His | missense_variant | Exon 9 of 11 | NP_001186628.1 | ||
DHX33 | XM_017024877.2 | c.362G>A | p.Arg121His | missense_variant | Exon 6 of 8 | XP_016880366.1 | ||
DHX33 | XM_047436418.1 | c.1518G>A | p.Pro506Pro | synonymous_variant | Exon 9 of 9 | XP_047292374.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251492Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135922
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727242
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74322
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1646G>A (p.R549H) alteration is located in exon 10 (coding exon 10) of the DHX33 gene. This alteration results from a G to A substitution at nucleotide position 1646, causing the arginine (R) at amino acid position 549 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at