Genetic Variant TFG:c.-287dupT (chr3-100709467-A-AT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001007565.2(TFG):c.-44+47dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 148,086 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.070 ( 0 hom. )

Consequence

TFG
NM_001007565.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.942

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

TFG links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007565.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TFG	NM_001007565.2		c.-44+47dupT	intron	N/A	NP_001007566.1	Q92734-1
TFG	NM_006070.6	MANE Select	c.-298_-297insT	upstream_gene	N/A	NP_006061.2
TFG	NM_001195478.2		c.-165_-164insT	upstream_gene	N/A	NP_001182407.1	Q92734-1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
TFG	ENST00000675692.1	c.-287dupT	5_prime_UTR	Exon 1 of 9	ENSP00000502034.1	A0A6Q8PFY7
TFG	ENST00000674615.1	c.-385dupT	5_prime_UTR	Exon 1 of 9	ENSP00000502734.1	Q92734-1
TFG	ENST00000675553.1	c.-154dupT	5_prime_UTR	Exon 1 of 8	ENSP00000501815.1	Q92734-1

Frequencies

GnomAD3 genomes

AF:

0.000643

AC:

AN:

147746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000666

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000336

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.00217

Gnomad SAS

AF:

0.00127

Gnomad FIN

AF:

0.000218

Gnomad MID

AF:

0.00662

Gnomad NFE

AF:

0.000615

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0695

AC:

AN:

302

Hom.:

Cov.:

AF XY:

0.0614

AC XY:

AN XY:

228

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0659

AC:

AN:

258

Other (OTH)

AF:

0.250

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.258

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000643

AC:

AN:

147784

Hom.:

Cov.:

AF XY:

0.000598

AC XY:

AN XY:

71892

show subpopulations

African (AFR)

AF:

0.000665

AC:

AN:

40606

American (AMR)

AF:

0.000336

AC:

AN:

14874

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

3436

East Asian (EAS)

AF:

0.00218

AC:

AN:

5042

South Asian (SAS)

AF:

0.00128

AC:

AN:

4704

European-Finnish (FIN)

AF:

0.000218

AC:

AN:

9182

Middle Eastern (MID)

AF:

0.00725

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.000615

AC:

AN:

66706

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.94

Mutation Taster

=100/0

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

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

3-100709467-ATTTTT-ATTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over