X-133217440-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016521.3(TFDP3):​c.820G>T​(p.Asp274Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control

Consequence

TFDP3
NM_016521.3 missense

Scores

6
2
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFDP3NM_016521.3 linkc.820G>T p.Asp274Tyr 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.820G>T p.Asp274Tyr missense_variant Exon 1 of 1 6 NM_016521.3 ENSP00000385461.1 Q5H9I0

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.00000547
AC:
1
AN:
182955
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67885
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:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
9.11e-7
AC:
1
AN:
1098077
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
1
AN XY:
363431
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:
0.00
Gnomad4 NFE exome
AF:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
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
Oct 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.820G>T (p.D274Y) alteration is located in exon 1 (coding exon 1) of the TFDP3 gene. This alteration results from a G to T substitution at nucleotide position 820, causing the aspartic acid (D) at amino acid position 274 to be replaced by a tyrosine (Y). 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
0.30
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
14
DANN
Benign
0.97
DEOGEN2
Uncertain
0.44
T
FATHMM_MKL
Benign
0.28
N
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.0075
T
MetaRNN
Pathogenic
0.95
D
MetaSVM
Benign
-0.77
T
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-8.4
D
REVEL
Uncertain
0.31
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.43
MutPred
0.93
Loss of disorder (P = 0.0247);
MVP
0.11
MPC
0.53
ClinPred
1.0
D
GERP RS
-0.41
Varity_R
0.49
gMVP
0.31

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.

Other links and lift over

dbSNP: rs370913906; hg19: chrX-132351468; API