NM_006070.6:c.594T>G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_006070.6(TFG):ā€‹c.594T>Gā€‹(p.Ala198Ala) 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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.57
Variant links:
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 Benign. Variant got -15 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.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFGNM_006070.6 linkc.594T>G p.Ala198Ala synonymous_variant Exon 6 of 8 ENST00000240851.9 NP_006061.2 Q92734-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TFGENST00000240851.9 linkc.594T>G p.Ala198Ala synonymous_variant Exon 6 of 8 1 NM_006070.6 ENSP00000240851.4 Q92734-1

Frequencies

GnomAD3 genomes
AF:
0.00404
AC:
615
AN:
152130
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00128
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.00433
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00207
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00716
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00442
AC:
1110
AN:
251178
Hom.:
2
AF XY:
0.00463
AC XY:
629
AN XY:
135736
show subpopulations
Gnomad AFR exome
AF:
0.00111
Gnomad AMR exome
AF:
0.00142
Gnomad ASJ exome
AF:
0.00387
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00183
Gnomad FIN exome
AF:
0.00185
Gnomad NFE exome
AF:
0.00767
Gnomad OTH exome
AF:
0.00603
GnomAD4 exome
AF:
0.00677
AC:
9899
AN:
1461690
Hom.:
34
Cov.:
31
AF XY:
0.00662
AC XY:
4817
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.00114
Gnomad4 AMR exome
AF:
0.00148
Gnomad4 ASJ exome
AF:
0.00367
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00211
Gnomad4 FIN exome
AF:
0.00251
Gnomad4 NFE exome
AF:
0.00808
Gnomad4 OTH exome
AF:
0.00651
GnomAD4 genome
AF:
0.00404
AC:
615
AN:
152248
Hom.:
2
Cov.:
32
AF XY:
0.00340
AC XY:
253
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.00128
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.00433
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00207
Gnomad4 NFE
AF:
0.00716
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00668
Hom.:
0
Bravo
AF:
0.00424
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00666
EpiControl
AF:
0.00717

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

TFG: BP4, BP7, BS2 -

Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Oct 19, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
Feb 10, 2025
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1
Jul 11, 2019
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
Jun 11, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
CADD
Benign
10
DANN
Benign
0.64
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12562; hg19: chr3-100455433; API