Variant 3-100744825-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006070.6(TFG):c.722-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00936 in 1,598,458 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 184 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 145 hom. )

Consequence

TFG
NM_006070.6 splice_region, intron

Scores

Splicing: ADA: 0.000007947

Clinical Significance

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

Conservation

PhyloP100: -1.23

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:

TFG (HGNC:):

TFG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-100744825-G-T is Benign according to our data. Variant chr3-100744825-G-T is described in ClinVar as [Benign]. Clinvar id is 378722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-100744825-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0896 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.722-8G>T		splice_region_variant, intron_variant		ENST00000240851.9	NP_006061.2	Q92734-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000240851.9 linkuse as main transcript	c.722-8G>T		splice_region_variant, intron_variant		1	NM_006070.6	ENSP00000240851.4		Q92734-1

Frequencies

GnomAD3 genomes

AF:

0.0297

AC:

4513

AN:

152004

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0920

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00651

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00531

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0111

AC:

2769

AN:

248642

Hom.:

AF XY:

0.00927

AC XY:

1246

AN XY:

134438

show subpopulations

Gnomad AFR exome

AF:

0.0983

Gnomad AMR exome

AF:

0.00659

Gnomad ASJ exome

AF:

0.000601

Gnomad EAS exome

AF:

0.00215

Gnomad SAS exome

AF:

0.00271

Gnomad FIN exome

AF:

0.00847

Gnomad NFE exome

AF:

0.00534

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00722

AC:

10440

AN:

1446336

Hom.:

145

Cov.:

AF XY:

0.00678

AC XY:

4883

AN XY:

720242

show subpopulations

Gnomad4 AFR exome

AF:

0.0918

Gnomad4 AMR exome

AF:

0.00797

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00114

Gnomad4 SAS exome

AF:

0.00252

Gnomad4 FIN exome

AF:

0.00829

Gnomad4 NFE exome

AF:

0.00517

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.0297

AC:

4524

AN:

152122

Hom.:

184

Cov.:

AF XY:

0.0287

AC XY:

2138

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0920

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00651

Gnomad4 NFE

AF:

0.00531

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0351

Asia WGS

AF:

0.00462

AC:

AN:

3478

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

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

-0.91

CADD

Benign

0.17

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000079

dbscSNV1_RF

Benign

0.0080

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