chr3-100709467-AT-A

Position:

• chr3-100709467-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000675692.1(TFG):​c.-287del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 148,022 control chromosomes in the GnomAD database, including 184 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (184 hom., cov: 32)
  • Exomes 𝑓: 0.058 (0 hom.)
• Consequence: TFG ENST00000675692.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.942

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-100709467-AT-A is Benign according to our data. Variant chr3-100709467-AT-A is described in ClinVar as [Benign]. Clinvar id is 1280370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFG	NM_006070.6			upstream_gene_variant		ENST00000240851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFG	ENST00000240851.9			upstream_gene_variant		1	NM_006070.6	P4

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4568 AN: 147692 Hom.: 183 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00582

Gnomad EAS AF: 0.00178

Gnomad SAS AF: 0.00296

Gnomad FIN AF: 0.00786

Gnomad MID AF: 0.00993

Gnomad NFE AF: 0.00576

Gnomad OTH AF: 0.0221

GnomAD4 exome AF: 0.0578 AC: 17 AN: 294 Hom.: 0 Cov.: 0 AF XY: 0.0541 AC XY: 12 AN XY: 222

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0591

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0310 AC: 4580 AN: 147728 Hom.: 184 Cov.: 32 AF XY: 0.0300 AC XY: 2156 AN XY: 71866

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00582

Gnomad4 EAS AF: 0.00179

Gnomad4 SAS AF: 0.00298

Gnomad4 FIN AF: 0.00786

Gnomad4 NFE AF: 0.00576

Gnomad4 OTH AF: 0.0220

Bravo AF: 0.0354

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 20, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs561497809; hg19: chr3-100428311;