3-100709512-A-G

Position:

• chr3-100709512-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BS1 BS2

The NM_006070.6(TFG):​c.-253A>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0227 in 151,694 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (54 hom., cov: 32)
  • Exomes 𝑓: 0.028 (0 hom.)
• Consequence: TFG NM_006070.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.09

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).
• BP6: Variant 3-100709512-A-G is Benign according to our data. Variant chr3-100709512-A-G is described in ClinVar as [Benign]. Clinvar id is 1291855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0227 (3436/151444) while in subpopulation NFE AF= 0.0291 (1970/67810). AF 95% confidence interval is 0.028. There are 54 homozygotes in gnomad4. There are 1760 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFG	NM_006070.6	c.-253A>G		5_prime_UTR_variant	1/8	ENST00000240851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFG	ENST00000240851.9	c.-253A>G		5_prime_UTR_variant	1/8	1	NM_006070.6	P4

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3439 AN: 151338 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.00472

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.00751

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00729

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.0280 AC: 7 AN: 250 Hom.: 0 Cov.: 0 AF XY: 0.0227 AC XY: 4 AN XY: 176

Gnomad4 AFR exome AF: 0.00

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: 0.0270

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0227 AC: 3436 AN: 151444 Hom.: 54 Cov.: 32 AF XY: 0.0238 AC XY: 1760 AN XY: 73996

Gnomad4 AFR AF: 0.00470

Gnomad4 AMR AF: 0.0253

Gnomad4 ASJ AF: 0.00751

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00731

Gnomad4 FIN AF: 0.0666

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0247 Hom.: 3

Bravo AF: 0.0199

Asia WGS AF: 0.00375 AC: 13 AN: 3478

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

Jun 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs114124529; hg19: chr3-100428356;