dbSNP rs561497809: TFG:c.-291_-287delTTTTT (chr3-100709467-ATTTTT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001007565.2(TFG):c.-44+43_-44+47delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 147,806 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 0.0000068 ( 0 hom., cov: 32)

Consequence

TFG
NM_001007565.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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+43_-44+47delTTTTT	intron	N/A	NP_001007566.1	Q92734-1
TFG	NM_006070.6	MANE Select	c.-297_-293delTTTTT	upstream_gene	N/A	NP_006061.2
TFG	NM_001195478.2		c.-164_-160delTTTTT	upstream_gene	N/A	NP_001182407.1	Q92734-1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
TFG	ENST00000675692.1	c.-291_-287delTTTTT	5_prime_UTR	Exon 1 of 9	ENSP00000502034.1	A0A6Q8PFY7
TFG	ENST00000674615.1	c.-389_-385delTTTTT	5_prime_UTR	Exon 1 of 9	ENSP00000502734.1	Q92734-1
TFG	ENST00000675553.1	c.-158_-154delTTTTT	5_prime_UTR	Exon 1 of 8	ENSP00000501815.1	Q92734-1

Frequencies

GnomAD3 genomes

AF:

0.00000677

AC:

AN:

147806

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:

0.0000150

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00000677

AC:

AN:

147806

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40532

American (AMR)

AF:

0.00

AC:

AN:

14864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5058

South Asian (SAS)

AF:

0.00

AC:

AN:

4724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66742

Other (OTH)

AF:

0.00

AC:

AN:

2034

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

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.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over