chr3-100744917-G-T

Position:

• chr3-100744917-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_006070.6(TFG):​c.806G>T​(p.Gly269Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFG NM_006070.6 missense
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• 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]

TFG (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823
• PP5: Variant 3-100744917-G-T is Pathogenic according to our data. Variant chr3-100744917-G-T is described in ClinVar as [Likely_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	Protein	UniProt
TFG	NM_006070.6	c.806G>T	p.Gly269Val	missense_variant	7/8	ENST00000240851.9	NP_006061.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFG	ENST00000240851.9	c.806G>T	p.Gly269Val	missense_variant	7/8	1	NM_006070.6	ENSP00000240851.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary motor and sensory neuropathy, Okinawa type Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 02, 2014

- -

Hereditary spastic paraplegia 57 Pathogenic:1

Likely pathogenic, no assertion criteria provided

provider interpretation

Solve-RD Consortium

Jun 01, 2022

Variant confirmed as disease-causing by referring clinical team -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	.;.;D;D;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;.;.;D;D;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.0	M;.;M;M;.;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.1	.;D;D;D;D;.
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0050	.;D;D;D;D;.
Sift4G	Uncertain	0.030	D;D;D;D;D;D
Polyphen		0.91	.;.;P;P;.;.
Vest4		0.71
MutPred		0.48		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		0.28
MPC		1.3
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.40
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.46		Position offset: -6

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;