3-100709616-G-C

Position:

• chr3-100709616-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006070.6(TFG):​c.-149G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 150,804 control chromosomes in the GnomAD database, including 34,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34238 hom., cov: 26)
  • Exomes 𝑓: 0.64 (11 hom.)
• Consequence: TFG NM_006070.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.342

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-100709616-G-C is Benign according to our data. Variant chr3-100709616-G-C is described in ClinVar as [Benign]. Clinvar id is 670587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFG	NM_006070.6	c.-149G>C		5_prime_UTR_variant	1/8	ENST00000240851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFG	ENST00000240851.9	c.-149G>C		5_prime_UTR_variant	1/8	1	NM_006070.6	P4

Frequencies

GnomAD3 genomes AF: 0.672 AC: 101210 AN: 150648 Hom.: 34191 Cov.: 26

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.702

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.662

GnomAD4 exome AF: 0.640 AC: 32 AN: 50 Hom.: 11 Cov.: 0 AF XY: 0.667 AC XY: 20 AN XY: 30

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.672 AC: 101317 AN: 150754 Hom.: 34238 Cov.: 26 AF XY: 0.675 AC XY: 49695 AN XY: 73616

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.666

Alfa AF: 0.674 Hom.: 4299

Bravo AF: 0.672

Asia WGS AF: 0.774 AC: 2684 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.5
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1059363; hg19: chr3-100428460;