rs766049461
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006070.6(TFG):c.1157C>T(p.Pro386Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
TFG
NM_006070.6 missense
NM_006070.6 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 4.30
Genes affected
TFG (HGNC:11758): (trafficking from ER to golgi regulator) There are several documented fusion oncoproteins encoded partially by this gene. This gene also participates in several oncogenic rearrangements resulting in anaplastic lymphoma and mixoid chondrosarcoma, and may play a role in the NF-kappaB pathway. Multiple transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]
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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=0.2182183).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFG | NM_006070.6 | c.1157C>T | p.Pro386Leu | missense_variant | 8/8 | ENST00000240851.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFG | ENST00000240851.9 | c.1157C>T | p.Pro386Leu | missense_variant | 8/8 | 1 | NM_006070.6 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250626Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135472
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461746Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727170
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary motor and sensory neuropathy, Okinawa type;C3714897:Hereditary spastic paraplegia 57 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TFG protein function. ClinVar contains an entry for this variant (Variation ID: 534745). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 386 of the TFG protein (p.Pro386Leu). This variant is present in population databases (rs766049461, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TFG-related conditions. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.0
.;B;B;.
Vest4
MutPred
0.49
.;Gain of glycosylation at Y381 (P = 0.0016);Gain of glycosylation at Y381 (P = 0.0016);.;
MVP
MPC
0.92
ClinPred
D
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