10-68901455-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024045.2(DDX50):​c.71A>T​(p.Lys24Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

DDX50
NM_024045.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0630
Variant links:
Genes affected
DDX50 (HGNC:17906): (DExD-box helicase 50) 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. This gene encodes a DEAD box enzyme that may be involved in ribosomal RNA synthesis or processing. This gene and DDX21, also called RH-II/GuA, have similar genomic structures and are in tandem orientation on chromosome 10, suggesting that the two genes arose by gene duplication in evolution. This gene has pseudogenes on chromosomes 2, 3 and 4. Alternative splicing of this gene generates multiple transcript variants, but the full length nature of all the other variants but one has not been defined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.107130766).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDX50NM_024045.2 linkuse as main transcriptc.71A>T p.Lys24Met missense_variant 1/15 ENST00000373585.8 NP_076950.1 Q9BQ39
DDX50XM_011540144.3 linkuse as main transcriptc.-179A>T 5_prime_UTR_premature_start_codon_gain_variant 1/16 XP_011538446.1
DDX50XM_011540144.3 linkuse as main transcriptc.-179A>T 5_prime_UTR_variant 1/16 XP_011538446.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDX50ENST00000373585.8 linkuse as main transcriptc.71A>T p.Lys24Met missense_variant 1/151 NM_024045.2 ENSP00000362687.3 Q9BQ39
DDX50ENST00000471475.1 linkuse as main transcriptn.71A>T non_coding_transcript_exon_variant 1/65 ENSP00000474314.1 S4R3G6
DDX50ENST00000483593.5 linkuse as main transcriptn.71A>T non_coding_transcript_exon_variant 1/73 ENSP00000474785.1 S4R3V4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMay 12, 2024The c.71A>T (p.K24M) alteration is located in exon 1 (coding exon 1) of the DDX50 gene. This alteration results from a A to T substitution at nucleotide position 71, causing the lysine (K) at amino acid position 24 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Benign
0.098
T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.036
Sift
Uncertain
0.0030
D
Sift4G
Benign
0.072
T
Polyphen
0.19
B
Vest4
0.31
MutPred
0.24
Loss of ubiquitination at K24 (P = 0.0107);
MVP
0.31
MPC
0.85
ClinPred
0.71
D
GERP RS
-2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.12
gMVP
0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-70661211; API