chr3-100709800-T-C

Position:

• chr3-100709800-T-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.-44+79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 146,266 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (173 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TFG NM_006070.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.635

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=-0.85).
• BP6: Variant 3-100709800-T-C is Benign according to our data. Variant chr3-100709800-T-C is described in ClinVar as [Benign]. Clinvar id is 1257482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.088 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFG	NM_006070.6	c.-44+79T>C		intron_variant		ENST00000240851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFG	ENST00000240851.9	c.-44+79T>C		intron_variant		1	NM_006070.6	P4

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4257 AN: 146154 Hom.: 172 Cov.: 23

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.00230

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.000587

Gnomad EAS AF: 0.00167

Gnomad SAS AF: 0.00315

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.00645

Gnomad NFE AF: 0.00521

Gnomad OTH AF: 0.0208

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 240 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR 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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0292 AC: 4267 AN: 146266 Hom.: 173 Cov.: 23 AF XY: 0.0283 AC XY: 2015 AN XY: 71296

Gnomad4 AFR AF: 0.0904

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.000587

Gnomad4 EAS AF: 0.00167

Gnomad4 SAS AF: 0.00315

Gnomad4 FIN AF: 0.00697

Gnomad4 NFE AF: 0.00521

Gnomad4 OTH AF: 0.0206

Alfa AF: 0.0219 Hom.: 19

Bravo AF: 0.0350

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 21, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.38
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: rs141580409; hg19: chr3-100428644;