Variant 3-141978677-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001178139.2(TFDP2):c.362G>A(p.Arg121Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TFDP2
NM_001178139.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	UniProt
TFDP2	NM_001178139.2 linkuse as main transcript	c.362G>A	p.Arg121Gln	missense_variant	7/13	ENST00000489671.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFDP2	ENST00000489671.6 linkuse as main transcript	c.362G>A	p.Arg121Gln	missense_variant	7/13	1	NM_001178139.2	P3	Q14188-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000425

AC:

AN:

235116

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127828

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000477

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1448106

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000198

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.362G>A (p.R121Q) alteration is located in exon 7 (coding exon 6) of the TFDP2 gene. This alteration results from a G to A substitution at nucleotide position 362, causing the arginine (R) at amino acid position 121 to be replaced by a glutamine (Q). 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

0.26

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.46

T;.;.;.;.;.;.;.;T;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

D;D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.48

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.2

M;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.1

D;.;D;D;D;D;D;D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0040

D;.;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.025

D;D;T;T;T;T;.;T;.;.

Polyphen

0.99

D;.;D;.;D;.;.;.;.;.

Vest4

0.64

MutPred

0.30

Gain of ubiquitination at K120 (P = 0.0331);.;.;.;.;.;.;.;.;.;

MVP

0.082

MPC

0.34

ClinPred

0.95

GERP RS

5.3

Varity_R

0.50

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over