Genetic Variant TFDP3:p.Glu240Gly (chrX-133217541-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016521.3(TFDP3):c.719A>G(p.Glu240Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,210,489 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 2 hem. )

Consequence

TFDP3
NM_016521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

TFDP3 (HGNC:24603): (transcription factor Dp family member 3) This gene encodes a member of the DP family of transcription factors. These factors heterodimerize with E2F proteins to enhance their DNA-binding activity and promote transcription from E2F target genes. This protein functions as a negative regulator and inhibits the DNA binding and transcriptional activities of E2F factors.[provided by RefSeq, May 2010]

TFDP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09868258).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFDP3	NM_016521.3 link	c.719A>G	p.Glu240Gly	missense_variant	Exon 1 of 1	ENST00000310125.5	NP_057605.3	Q5H9I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFDP3	ENST00000310125.5 link	c.719A>G	p.Glu240Gly	missense_variant	Exon 1 of 1	6	NM_016521.3	ENSP00000385461.1		Q5H9I0

Frequencies

GnomAD3 genomes

AF:

0.0000534

AC:

AN:

112287

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34433

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000939

Gnomad OTH

AF:

0.000658

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

182933

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67833

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:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1098202

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00000950

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000534

AC:

AN:

112287

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34433

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000939

Gnomad4 OTH

AF:

0.000658

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.719A>G (p.E240G) alteration is located in exon 1 (coding exon 1) of the TFDP3 gene. This alteration results from a A to G substitution at nucleotide position 719, causing the glutamic acid (E) at amino acid position 240 to be replaced by a glycine (G). 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

0.080

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.065

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.21

M_CAP

Benign

0.0016

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.10

Sift

Benign

0.042

Sift4G

Uncertain

0.021

Polyphen

0.15

Vest4

0.076

MVP

0.081

MPC

0.25

ClinPred

0.19

GERP RS

0.21

Varity_R

0.12

gMVP

0.053

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

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