3-142005508-G-A

Position:

• chr3-142005508-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001178139.2(TFDP2):​c.119C>T​(p.Thr40Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFDP2 NM_001178139.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40

Genes affected

TFDP2 (HGNC:11751): (transcription factor Dp-2) The gene is a member of the transcription factor DP family. The encoded protein forms heterodimers with the E2F transcription factors resulting in transcriptional activation of cell cycle regulated genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

TFDP2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11022234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFDP2	NM_001178139.2	c.119C>T	p.Thr40Ile	missense_variant	4/13	ENST00000489671.6	NP_001171610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFDP2	ENST00000489671.6	c.119C>T	p.Thr40Ile	missense_variant	4/13	1	NM_001178139.2	ENSP00000420616.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.119C>T (p.T40I) alteration is located in exon 4 (coding exon 3) of the TFDP2 gene. This alteration results from a C to T substitution at nucleotide position 119, causing the threonine (T) at amino acid position 40 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.0062
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.023
Sift	Benign	0.29	T;T
Sift4G	Benign	0.46	T;.
Polyphen		0.023	B;.
Vest4		0.28
MutPred		0.22		Loss of glycosylation at T40 (P = 0.0253);Loss of glycosylation at T40 (P = 0.0253);
MVP		0.043
MPC		0.31
ClinPred		0.36	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-141724350; COSMIC: COSV57711585; COSMIC: COSV57711585;