rs373067235

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020162.4(DHX33):​c.1646G>T​(p.Arg549Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R549C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DHX33
NM_020162.4 missense

Scores

9
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.46
Variant links:
Genes affected
DHX33 (HGNC:16718): (DEAH-box helicase 33) This gene encodes a member of the DEAD box protein family. The DEAD box proteins are 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

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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, 0.867

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DHX33NM_020162.4 linkc.1646G>T p.Arg549Leu missense_variant Exon 10 of 12 ENST00000225296.8 NP_064547.2 Q9H6R0-1B4DIS6
DHX33NM_001199699.2 linkc.1127G>T p.Arg376Leu missense_variant Exon 9 of 11 NP_001186628.1 Q9H6R0-2B4DIS6
DHX33XM_017024877.2 linkc.362G>T p.Arg121Leu missense_variant Exon 6 of 8 XP_016880366.1 Q9H6R0
DHX33XM_047436418.1 linkc.1518G>T p.Pro506Pro synonymous_variant Exon 9 of 9 XP_047292374.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DHX33ENST00000225296.8 linkc.1646G>T p.Arg549Leu missense_variant Exon 10 of 12 1 NM_020162.4 ENSP00000225296.3 Q9H6R0-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251492
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461884
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.097
T;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Benign
-0.63
T
MutationAssessor
Pathogenic
3.3
M;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Uncertain
0.56
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.037
D;D
Polyphen
0.99
D;P
Vest4
0.94
MutPred
0.67
Loss of disorder (P = 0.0249);.;
MVP
0.77
MPC
0.96
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.79
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373067235; hg19: chr17-5353605; API