chr6-73401928-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018665.3(DDX43):​c.506C>T​(p.Pro169Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

DDX43
NM_018665.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49
Variant links:
Genes affected
DDX43 (HGNC:18677): (DEAD-box helicase 43) The protein encoded by this gene is an ATP-dependent RNA helicase in the DEAD-box family and displays tumor-specific expression. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27904826).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDX43NM_018665.3 linkuse as main transcriptc.506C>T p.Pro169Leu missense_variant 4/17 ENST00000370336.5 NP_061135.2 Q9NXZ2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDX43ENST00000370336.5 linkuse as main transcriptc.506C>T p.Pro169Leu missense_variant 4/171 NM_018665.3 ENSP00000359361.4 Q9NXZ2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
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 GeneticsSep 10, 2024The c.506C>T (p.P169L) alteration is located in exon 4 (coding exon 4) of the DDX43 gene. This alteration results from a C to T substitution at nucleotide position 506, causing the proline (P) at amino acid position 169 to be replaced by a leucine (L). 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
0.091
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.048
T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.9
M
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-6.3
D
REVEL
Benign
0.13
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.023
D
Polyphen
0.26
B
Vest4
0.34
MutPred
0.46
Loss of loop (P = 0.1242);
MVP
0.49
MPC
0.76
ClinPred
0.97
D
GERP RS
3.8
Varity_R
0.16
gMVP
0.089

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: chr6-74111651; API