chr3-100713641-AG-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_006070.6(TFG):c.-43-1del variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,345,604 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
TFG
NM_006070.6 splice_acceptor
NM_006070.6 splice_acceptor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.350
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]
Genome browser will be placed here
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;
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000352 (42/1193384) while in subpopulation AMR AF= 0.0017 (42/24742). AF 95% confidence interval is 0.00129. There are 0 homozygotes in gnomad4_exome. There are 21 alleles in male gnomad4_exome subpopulation. Median coverage is 17. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFG | NM_006070.6 | c.-43-1del | splice_acceptor_variant | ENST00000240851.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFG | ENST00000240851.9 | c.-43-1del | splice_acceptor_variant | 1 | NM_006070.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152102Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
8
AN:
152102
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000260 AC: 44AN: 169166Hom.: 0 AF XY: 0.000227 AC XY: 21AN XY: 92382
GnomAD3 exomes
AF:
AC:
44
AN:
169166
Hom.:
AF XY:
AC XY:
21
AN XY:
92382
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000352 AC: 42AN: 1193384Hom.: 0 Cov.: 17 AF XY: 0.0000359 AC XY: 21AN XY: 584234
GnomAD4 exome
AF:
AC:
42
AN:
1193384
Hom.:
Cov.:
17
AF XY:
AC XY:
21
AN XY:
584234
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74428
GnomAD4 genome
?
AF:
AC:
8
AN:
152220
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74428
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 26, 2017 | A variant of uncertain significance has been identified in the TFG gene. The c.-43-1delG variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.-43-1delG splice site variant destroys the canonical splice acceptor site in intron 1. It is predicted to cause abnormal gene splicing. However, the c.-43-1delG variant is observed in 37/11,506 (0.3%) alleles from individuals of Latino background in large population cohorts, which is greater than expected for this disorder (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, this deletion occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 13
DS_AL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at