chr19-12701386-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2
The NM_001382241.1(TNPO2):c.2654C>T(p.Pro885Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 0 hom. )
Consequence
TNPO2
NM_001382241.1 missense
NM_001382241.1 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 5.26
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 Benign. Variant got -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TNPO2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08073914).
BP6
?
Variant 19-12701386-G-A is Benign according to our data. Variant chr19-12701386-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3180549.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNPO2 | NM_001382241.1 | c.2654C>T | p.Pro885Leu | missense_variant | 25/26 | ENST00000425528.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNPO2 | ENST00000425528.6 | c.2654C>T | p.Pro885Leu | missense_variant | 25/26 | 5 | NM_001382241.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152140Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000843 AC: 21AN: 249182Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135208
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GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461684Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727128
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74446
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 17, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.;.;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;L;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;.;.;.;.
REVEL
Uncertain
Sift
Benign
T;T;.;.;.;.
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;.;.;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at