19-12703776-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate
The NM_001382241.1(TNPO2):c.2048G>C(p.Ser683Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TNPO2
NM_001382241.1 missense
NM_001382241.1 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 7.36
Genes affected
TNPO2 (HGNC:19998): (transportin 2) Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Predicted to be involved in protein import into nucleus. Predicted to act upstream of or within negative regulation of muscle cell differentiation. Predicted to be active in cytoplasm and 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 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the TNPO2 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 11 curated pathogenic missense variants (we use a threshold of 10). The gene has 5 curated benign missense variants. Gene score misZ: 5.8776 (above the threshold of 3.09). Trascript score misZ: 6.7753 (above the threshold of 3.09). GenCC associations: The gene is linked to intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies.
PP5
Variant 19-12703776-C-G is Pathogenic according to our data. Variant chr19-12703776-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1308660.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TNPO2 | NM_001382241.1 | c.2048G>C | p.Ser683Thr | missense_variant | 19/26 | ENST00000425528.6 | NP_001369170.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies Pathogenic:1
| Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Oct 28, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;.;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H;H;H;H
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;.;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;.;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;.;.;D;.
Vest4
MutPred
Loss of disorder (P = 0.0557);Loss of disorder (P = 0.0557);Loss of disorder (P = 0.0557);Loss of disorder (P = 0.0557);Loss of disorder (P = 0.0557);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.