NM_006070.6:c.-44+79T>C

Variant names:

• chr3-100709800-T-C
• rs141580409
• NM_006070.6:c.-44+79T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006070.6(TFG):​c.-44+79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 146,266 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (173 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TFG NM_006070.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.635
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-100709800-T-C is Benign according to our data. Variant chr3-100709800-T-C is described in ClinVar as Benign. ClinVar VariationId is 1257482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.088 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFG	NM_006070.6	MANE Select	c.-44+79T>C		intron	N/A	NP_006061.2
	TFG	NM_001007565.2		c.-44+369T>C		intron	N/A	NP_001007566.1	Q92734-1
	TFG	NM_001195478.2		c.-44+212T>C		intron	N/A	NP_001182407.1	Q92734-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFG	ENST00000240851.9	TSL:1 MANE Select	c.-44+79T>C		intron	N/A	ENSP00000240851.4	Q92734-1
	TFG	ENST00000476228.5	TSL:1	c.-44+79T>C		intron	N/A	ENSP00000417952.1	Q92734-2
	TFG	ENST00000676395.1		c.-65T>C		5_prime_UTR	Exon 1 of 8	ENSP00000502071.1	Q92734-1

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4257 AN: 146154 Hom.: 172 Cov.: 23

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.00230

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.000587

Gnomad EAS AF: 0.00167

Gnomad SAS AF: 0.00315

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.00645

Gnomad NFE AF: 0.00521

Gnomad OTH AF: 0.0208

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 240 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 192

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 206

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.0292 AC: 4267 AN: 146266 Hom.: 173 Cov.: 23 AF XY: 0.0283 AC XY: 2015 AN XY: 71296

African (AFR) AF: 0.0904 AC: 3583 AN: 39622

American (AMR) AF: 0.0136 AC: 202 AN: 14892

Ashkenazi Jewish (ASJ) AF: 0.000587 AC: 2 AN: 3406

East Asian (EAS) AF: 0.00167 AC: 8 AN: 4786

South Asian (SAS) AF: 0.00315 AC: 14 AN: 4444

European-Finnish (FIN) AF: 0.00697 AC: 68 AN: 9754

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.00521 AC: 345 AN: 66210

Other (OTH) AF: 0.0206 AC: 41 AN: 1994

Alfa AF: 0.0219 Hom.: 19

Bravo AF: 0.0350

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.38
PhyloP100		-0.64
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs141580409; hg19: chr3-100428644;