chr3-100714748-T-C

Variant names:

• chr3-100714748-T-C
• rs591728
• NM_006070.6:c.184+879T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006070.6(TFG):​c.184+879T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,094 control chromosomes in the GnomAD database, including 5,417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5417 hom., cov: 33)
• Consequence: TFG NM_006070.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 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.184+879T>C		intron	N/A	NP_006061.2
	TFG	NM_001007565.2		c.184+879T>C		intron	N/A	NP_001007566.1	Q92734-1
	TFG	NM_001195478.2		c.184+879T>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.184+879T>C		intron	N/A	ENSP00000240851.4	Q92734-1
	TFG	ENST00000476228.5	TSL:1	c.184+879T>C		intron	N/A	ENSP00000417952.1	Q92734-2
	TFG	ENST00000615993.2	TSL:1	c.184+879T>C		intron	N/A	ENSP00000479269.2	Q92734-4

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37063 AN: 151976 Hom.: 5425 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.244 AC: 37048 AN: 152094 Hom.: 5417 Cov.: 33 AF XY: 0.239 AC XY: 17772 AN XY: 74346

African (AFR) AF: 0.115 AC: 4757 AN: 41538

American (AMR) AF: 0.210 AC: 3206 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3470

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5190

South Asian (SAS) AF: 0.150 AC: 721 AN: 4820

European-Finnish (FIN) AF: 0.297 AC: 3132 AN: 10550

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.336 AC: 22844 AN: 67930

Other (OTH) AF: 0.259 AC: 547 AN: 2112

Alfa AF: 0.303 Hom.: 3885

Bravo AF: 0.233

Asia WGS AF: 0.0870 AC: 305 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs591728; hg19: chr3-100433592;