rs149927288

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_006070.6(TFG):c.415+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,596,198 control chromosomes in the GnomAD database, including 2 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

TFG
NM_006070.6 splice_region, intron

Scores

Splicing: ADA: 0.00005289

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.03

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-100728865-C-G is Benign according to our data. Variant chr3-100728865-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 466409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006070.6. 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_006070.6	MANE Select	c.415+7C>G	splice_region intron	N/A	NP_006061.2
TFG	NM_001007565.2		c.415+7C>G	splice_region intron	N/A	NP_001007566.1	Q92734-1
TFG	NM_001195478.2		c.415+7C>G	splice_region intron	N/A	NP_001182407.1	Q92734-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TFG	ENST00000240851.9	TSL:1 MANE Select	c.415+7C>G	splice_region intron	N/A	ENSP00000240851.4	Q92734-1
TFG	ENST00000476228.5	TSL:1	c.415+7C>G	splice_region intron	N/A	ENSP00000417952.1	Q92734-2
TFG	ENST00000615993.2	TSL:1	c.415+7C>G	splice_region intron	N/A	ENSP00000479269.2	Q92734-4

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000286

AC:

AN:

234158

AF XY:

0.000228

show subpopulations

Gnomad AFR exome

AF:

0.00430

Gnomad AMR exome

AF:

0.0000333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

149

AN:

1443988

Hom.:

Cov.:

AF XY:

0.0000988

AC XY:

AN XY:

718586

show subpopulations

African (AFR)

AF:

0.00383

AC:

123

AN:

32148

American (AMR)

AF:

0.000148

AC:

AN:

40666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25406

East Asian (EAS)

AF:

0.00

AC:

AN:

38792

South Asian (SAS)

AF:

0.00

AC:

AN:

83402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53098

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105190

Other (OTH)

AF:

0.000319

AC:

AN:

59600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152210

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00388

AC:

161

AN:

41538

American (AMR)

AF:

0.000262

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.000293

Hom.:

Bravo

AF:

0.00111

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary motor and sensory neuropathy, Okinawa type;C3714897:Hereditary spastic paraplegia 57 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.085

(source)

DANN

Benign

0.52

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000053

dbscSNV1_RF

Benign

0.0040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over