rs12562
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_006070.6(TFG):āc.594T>Gā(p.Ala198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00651 in 1,613,938 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0040 ( 2 hom., cov: 32)
Exomes š: 0.0068 ( 34 hom. )
Consequence
TFG
NM_006070.6 synonymous
NM_006070.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.57
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 Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 3-100736589-T-G is Benign according to our data. Variant chr3-100736589-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 466410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-100736589-T-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.57 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00404 (615/152248) while in subpopulation NFE AF= 0.00716 (487/68022). AF 95% confidence interval is 0.00663. There are 2 homozygotes in gnomad4. There are 253 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TFG | NM_006070.6 | c.594T>G | p.Ala198= | synonymous_variant | 6/8 | ENST00000240851.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TFG | ENST00000240851.9 | c.594T>G | p.Ala198= | synonymous_variant | 6/8 | 1 | NM_006070.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00404 AC: 615AN: 152130Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00442 AC: 1110AN: 251178Hom.: 2 AF XY: 0.00463 AC XY: 629AN XY: 135736
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GnomAD4 exome AF: 0.00677 AC: 9899AN: 1461690Hom.: 34 Cov.: 31 AF XY: 0.00662 AC XY: 4817AN XY: 727138
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GnomAD4 genome ? AF: 0.00404 AC: 615AN: 152248Hom.: 2 Cov.: 32 AF XY: 0.00340 AC XY: 253AN XY: 74422
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 19, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | TFG: BP4, BP7, BS2 - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | 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. - |
TFG-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 11, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary motor and sensory neuropathy, Okinawa type;C3714897:Hereditary spastic paraplegia 57 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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