X-133218025-G-T

Variant names:

• chrX-133218025-G-T
• NM_016521.3:c.235C>A

Variant summary

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

The NM_016521.3(TFDP3):​c.235C>A​(p.Pro79Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TFDP3 NM_016521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12

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]

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=0.21374932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFDP3	NM_016521.3	c.235C>A	p.Pro79Thr	missense_variant	Exon 1 of 1	ENST00000310125.5	NP_057605.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFDP3	ENST00000310125.5	c.235C>A	p.Pro79Thr	missense_variant	Exon 1 of 1	6	NM_016521.3	ENSP00000385461.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.235C>A (p.P79T) alteration is located in exon 1 (coding exon 1) of the TFDP3 gene. This alteration results from a C to A substitution at nucleotide position 235, causing the proline (P) at amino acid position 79 to be replaced by a threonine (T). 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	0.077
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.16
Sift	Benign	0.044	D
Sift4G	Benign	0.13	T
Polyphen		0.93	P
Vest4		0.15
MutPred		0.28		Loss of glycosylation at P79 (P = 0.0723);
MVP		0.13
MPC		0.79
ClinPred		0.59	D
GERP RS		0.23
Varity_R		0.13
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chrX-132352053; COSMIC: COSV59537926;