3-100709467-ATTTTT-ATTTTTT

Variant names:

• chr3-100709467-A-AT
• rs561497809
• ENST00000675692:c.-287dupT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001007565.2(TFG):​c.-44+47dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 148,086 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 0.00064 (0 hom., cov: 32)
  • Exomes 𝑓: 0.070 (0 hom.)
• Consequence: TFG NM_001007565.2 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0695 (21/302) while in subpopulation AFR AF= 0.167 (2/12). AF 95% confidence interval is 0.042. There are 0 homozygotes in gnomad4_exome. There are 14 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFG	NM_006070.6	c.-298_-297insT		upstream_gene_variant		ENST00000240851.9	NP_006061.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000240851.9	c.-298_-297insT		upstream_gene_variant		1	NM_006070.6	ENSP00000240851.4

Frequencies

GnomAD3 genomes AF: 0.000643 AC: 95 AN: 147746 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000336

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00217

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.000218

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.000615

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0695 AC: 21 AN: 302 Hom.: 0 Cov.: 0 AF XY: 0.0614 AC XY: 14 AN XY: 228

Gnomad4 AFR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0659

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.000643 AC: 95 AN: 147784 Hom.: 0 Cov.: 32 AF XY: 0.000598 AC XY: 43 AN XY: 71892

Gnomad4 AFR AF: 0.000665

Gnomad4 AMR AF: 0.000336

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.00218

Gnomad4 SAS AF: 0.00128

Gnomad4 FIN AF: 0.000218

Gnomad4 NFE AF: 0.000615

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs561497809; hg19: chr3-100428311;