19-18922377-G-A

Variant summary

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

The NM_019070.5(DDX49):​c.499G>A​(p.Val167Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,459,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

DDX49
NM_019070.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98
Variant links:
Genes affected
DDX49 (HGNC:18684): (DEAD-box helicase 49) Enables RNA binding activity. Involved in positive regulation of cell growth and regulation of rRNA stability. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.12751284).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDX49NM_019070.5 linkuse as main transcriptc.499G>A p.Val167Met missense_variant 5/13 ENST00000247003.9 NP_061943.2 Q9Y6V7-1
DDX49XM_011528084.4 linkuse as main transcriptc.178G>A p.Val60Met missense_variant 6/14 XP_011526386.1
DDX49NR_033677.2 linkuse as main transcriptn.455G>A non_coding_transcript_exon_variant 5/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDX49ENST00000247003.9 linkuse as main transcriptc.499G>A p.Val167Met missense_variant 5/131 NM_019070.5 ENSP00000247003.3 Q9Y6V7-1
ENSG00000268193ENST00000596918.5 linkuse as main transcriptn.*167+8948C>T intron_variant 5 ENSP00000469669.1 M0R1B8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000824
AC:
2
AN:
242810
Hom.:
0
AF XY:
0.00000756
AC XY:
1
AN XY:
132310
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:
0.0000183
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1459444
Hom.:
0
Cov.:
33
AF XY:
0.00000826
AC XY:
6
AN XY:
726002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

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 GeneticsDec 15, 2023The c.499G>A (p.V167M) alteration is located in exon 5 (coding exon 5) of the DDX49 gene. This alteration results from a G to A substitution at nucleotide position 499, causing the valine (V) at amino acid position 167 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
0.081
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
16
DANN
Uncertain
0.97
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.14
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.020
N
REVEL
Benign
0.044
Sift
Benign
0.081
T
Sift4G
Benign
0.096
T
Polyphen
0.12
B
Vest4
0.22
MutPred
0.45
Gain of helix (P = 0.2059);
MVP
0.13
MPC
0.66
ClinPred
0.045
T
GERP RS
-0.018
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.042
gMVP
0.40

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: rs774272419; hg19: chr19-19033186; API