X-133217509-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016521.3(TFDP3):​c.751G>A​(p.Val251Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,210,474 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.0000064 ( 0 hom. 1 hem. )

Consequence

TFDP3
NM_016521.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.947
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08103895).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFDP3NM_016521.3 linkc.751G>A p.Val251Ile 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
TFDP3ENST00000310125.5 linkc.751G>A p.Val251Ile missense_variant Exon 1 of 1 6 NM_016521.3 ENSP00000385461.1 Q5H9I0

Frequencies

GnomAD3 genomes
AF:
0.00000891
AC:
1
AN:
112230
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34376
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000944
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000218
AC:
4
AN:
183097
Hom.:
0
AF XY:
0.0000147
AC XY:
1
AN XY:
67861
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.000134
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000524
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000637
AC:
7
AN:
1098244
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
1
AN XY:
363598
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000568
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000868
GnomAD4 genome
AF:
0.00000891
AC:
1
AN:
112230
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34376
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000944
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.751G>A (p.V251I) alteration is located in exon 1 (coding exon 1) of the TFDP3 gene. This alteration results from a G to A substitution at nucleotide position 751, causing the valine (V) at amino acid position 251 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
0.087
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.98
CADD
Benign
1.9
DANN
Benign
0.42
DEOGEN2
Benign
0.0047
T
FATHMM_MKL
Benign
0.15
N
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.52
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.76
N
REVEL
Benign
0.020
Sift
Benign
0.36
T
Sift4G
Benign
0.34
T
Polyphen
0.0070
B
Vest4
0.054
MVP
0.030
MPC
0.16
ClinPred
0.024
T
GERP RS
0.21
Varity_R
0.048
gMVP
0.031

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.

Other links and lift over

dbSNP: rs373819303; hg19: chrX-132351537; API