rs35648279

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006070.6(TFG):c.552G>A(p.Ala184Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00946 in 1,611,108 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A184A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.030 ( 184 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 205 hom. )

Consequence

TFG
NM_006070.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.740

Publications

2 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 3-100732644-G-A is Benign according to our data. Variant chr3-100732644-G-A is described in ClinVar as Benign. ClinVar VariationId is 378720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFG	NM_006070.6 link	c.552G>A	p.Ala184Ala	synonymous_variant	Exon 5 of 8	ENST00000240851.9	NP_006061.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000240851.9 link	c.552G>A	p.Ala184Ala	synonymous_variant	Exon 5 of 8	1	NM_006070.6	ENSP00000240851.4

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4537

AN:

152126

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0924

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00670

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00532

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0112

AC:

2789

AN:

248312

AF XY:

0.00936

show subpopulations

Gnomad AFR exome

AF:

0.0993

Gnomad AMR exome

AF:

0.00682

Gnomad ASJ exome

AF:

0.000599

Gnomad EAS exome

AF:

0.00214

Gnomad FIN exome

AF:

0.00849

Gnomad NFE exome

AF:

0.00538

Gnomad OTH exome

AF:

0.00779

GnomAD4 exome

AF:

0.00733

AC:

10690

AN:

1458864

Hom.:

205

Cov.:

AF XY:

0.00690

AC XY:

5005

AN XY:

725770

show subpopulations

African (AFR)

AF:

0.0946

AC:

3148

AN:

33284

American (AMR)

AF:

0.00811

AC:

359

AN:

44274

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

26056

East Asian (EAS)

AF:

0.00119

AC:

AN:

39438

South Asian (SAS)

AF:

0.00257

AC:

221

AN:

85826

European-Finnish (FIN)

AF:

0.00838

AC:

447

AN:

53336

Middle Eastern (MID)

AF:

0.00714

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00520

AC:

5779

AN:

1110654

Other (OTH)

AF:

0.0101

AC:

611

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

453

906

1360

1813

2266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.0299

AC:

4548

AN:

152244

Hom.:

184

Cov.:

AF XY:

0.0288

AC XY:

2145

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0924

AC:

3836

AN:

41534

American (AMR)

AF:

0.0136

AC:

208

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00174

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00670

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00532

AC:

362

AN:

68020

Other (OTH)

AF:

0.0199

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

209

419

628

838

1047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.0352

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00533

EpiControl

AF:

0.00514

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 30, 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

Apr 17, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Benign:1

Feb 03, 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

-0.53

CADD

Benign

2.8

(source)

DANN

Benign

0.69

PhyloP100

-0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over