rs587777789

chr3-100744917-G-Achr3-100744917-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_006070.6(TFG):c.806G>A(p.Gly269Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,374 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G269V) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TFG NM_006070.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.43

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr3-100744917-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 156445.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFG	NM_006070.6	c.806G>A	p.Gly269Asp	missense_variant	7/8	ENST00000240851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFG	ENST00000240851.9	c.806G>A	p.Gly269Asp	missense_variant	7/8	1	NM_006070.6	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250546 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135396

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459374 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Uncertain	-0.070
Cadd	Pathogenic	28
Dann	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.74	D;D;D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.0	M;.;M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.67	T
Sift4G	Uncertain	0.060	T;D;T;T;D;T
Polyphen		0.95	.;.;P;P;.;.
Vest4		0.68
MutPred		0.51		Loss of glycosylation at P265 (P = 0.0107);.;Loss of glycosylation at P265 (P = 0.0107);Loss of glycosylation at P265 (P = 0.0107);.;Loss of glycosylation at P265 (P = 0.0107);
MVP		0.34
MPC		1.3
ClinPred		0.65	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.21

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: rs587777789; hg19: chr3-100463761; COSMIC: COSV52547564; COSMIC: COSV52547564;