Variant chr3-100732644-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006070.6(TFG):c.552G>A(p.Ala184=) 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 (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 378720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-100732644-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
TFG	NM_006070.6 linkuse as main transcript	c.552G>A	p.Ala184=	synonymous_variant	5/8	ENST00000240851.9	NP_006061.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000240851.9 linkuse as main transcript	c.552G>A	p.Ala184=	synonymous_variant	5/8	1	NM_006070.6	ENSP00000240851	P4	Q92734-1

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

GnomAD3 exomes

AF:

0.0112

AC:

2789

AN:

248312

Hom.:

AF XY:

0.00936

AC XY:

1257

AN XY:

134328

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 SAS exome

AF:

0.00272

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

Gnomad4 AFR exome

AF:

0.0946

Gnomad4 AMR exome

AF:

0.00811

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00119

Gnomad4 SAS exome

AF:

0.00257

Gnomad4 FIN exome

AF:

0.00838

Gnomad4 NFE exome

AF:

0.00520

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.0299

AC:

4548

AN:

152244

Hom.:

184

Cov.:

AF XY:

0.0288

AC XY:

2145

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0924

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00670

Gnomad4 NFE

AF:

0.00532

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0131

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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 30, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 17, 2015

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.8

DANN

Benign

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over