chr3-100748308-A-C

Position:

• chr3-100748308-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006070.6(TFG):​c.980A>C​(p.Gln327Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFG NM_006070.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.38

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]

TFG (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFG	NM_006070.6	c.980A>C	p.Gln327Pro	missense_variant	8/8	ENST00000240851.9	NP_006061.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000240851.9	c.980A>C	p.Gln327Pro	missense_variant	8/8	1	NM_006070.6	ENSP00000240851.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;T;T;.
Eigen	Benign	-0.047
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	.;M;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.13	N;N;N;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.61
MutPred		0.31		.;Gain of glycosylation at Y329 (P = 0.0078);Gain of glycosylation at Y329 (P = 0.0078);.;
MVP		0.50
MPC		0.56
ClinPred		0.78	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.49

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: rs1431898500; hg19: chr3-100467152;