X-133218077-C-A

Variant summary

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

The NM_016521.3(TFDP3):​c.183G>T​(p.Met61Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,209,449 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.0000090 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000082 ( 0 hom. 2 hem. )

Consequence

TFDP3
NM_016521.3 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.670
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_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.096251726).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFDP3NM_016521.3 linkc.183G>T p.Met61Ile 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.183G>T p.Met61Ile missense_variant Exon 1 of 1 6 NM_016521.3 ENSP00000385461.1 Q5H9I0

Frequencies

GnomAD3 genomes
AF:
0.00000898
AC:
1
AN:
111355
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33549
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:
0.00
Gnomad OTH
AF:
0.000670
GnomAD3 exomes
AF:
0.0000164
AC:
3
AN:
183130
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67576
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000722
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000442
GnomAD4 exome
AF:
0.00000820
AC:
9
AN:
1098094
Hom.:
0
Cov.:
34
AF XY:
0.00000550
AC XY:
2
AN XY:
363450
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000993
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000130
GnomAD4 genome
AF:
0.00000898
AC:
1
AN:
111355
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33549
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:
0.00
Gnomad4 OTH
AF:
0.000670
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.183G>T (p.M61I) 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 183, causing the methionine (M) at amino acid position 61 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
0.24
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
8.0
DANN
Benign
0.96
DEOGEN2
Benign
0.0055
T
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.096
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.77
N
REVEL
Benign
0.028
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.026
D
Polyphen
0.12
B
Vest4
0.15
MutPred
0.47
Loss of catalytic residue at M61 (P = 0.0066);
MVP
0.39
MPC
0.27
ClinPred
0.055
T
GERP RS
0.23
Varity_R
0.29
gMVP
0.079

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: rs371634842; hg19: chrX-132352105; API