rs963151000

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_006070.6(TFG):c.1199G>A(p.Arg400Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,609,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R400P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

TFG
NM_006070.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.07

Publications

0 publications found

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]

TFG Gene-Disease associations (from GenCC):

hereditary motor and sensory neuropathy, Okinawa type
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
hereditary spastic paraplegia 57
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TFG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 3-100748527-G-A is Benign according to our data. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-100748527-G-A is described in CliVar as Likely_benign. Clinvar id is 581201.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFG	NM_006070.6 link	c.1199G>A	p.Arg400Gln	missense_variant	Exon 8 of 8	ENST00000240851.9	NP_006061.2	Q92734-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000240851.9 link	c.1199G>A	p.Arg400Gln	missense_variant	Exon 8 of 8	1	NM_006070.6	ENSP00000240851.4		Q92734-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247544

AF XY:

0.00000747

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1457438

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25858

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

85972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00000812

AC:

AN:

1108934

Other (OTH)

AF:

0.00

AC:

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000285

Hom.:

Bravo

AF:

0.0000302

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary motor and sensory neuropathy, Okinawa type;C3714897:Hereditary spastic paraplegia 57

Benign:1

Feb 14, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

.;T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;.;D;D

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.72

D;D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

.;L;L;.

PhyloP100

9.1

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.18

N;N;N;N

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.91

.;P;P;.

Vest4

0.90

MutPred

0.40

.;Loss of methylation at R400 (P = 0.0214);Loss of methylation at R400 (P = 0.0214);.;

MVP

0.75

MPC

0.59

ClinPred

0.79

GERP RS

5.3

Varity_R

0.30

gMVP

0.23

Mutation Taster

=65/35

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over