dbSNP rs373819303: TFDP3:p.Val251Phe (chrX-133217509-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016521.3(TFDP3):c.751G>T(p.Val251Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,210,474 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V251I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

TFDP3
NM_016521.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.947

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15670681).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFDP3	NM_016521.3 link	c.751G>T	p.Val251Phe	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.751G>T	p.Val251Phe	missense_variant	Exon 1 of 1	6	NM_016521.3	ENSP00000385461.1		Q5H9I0

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112230

Hom.:

Cov.:

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:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000546

AC:

AN:

183097

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1098244

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363598

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

842133

Other (OTH)

AF:

0.00

AC:

AN:

46097

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112230

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30881

American (AMR)

AF:

0.00

AC:

AN:

10598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.00

AC:

AN:

3576

South Asian (SAS)

AF:

0.00

AC:

AN:

2685

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6109

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000563

AC:

AN:

53285

Other (OTH)

AF:

0.00

AC:

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.058

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0020

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

0.95

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.064

Sift

Benign

0.28

Sift4G

Uncertain

0.052

Polyphen

0.36

Vest4

0.19

MutPred

0.43

Gain of glycosylation at P248 (P = 0.1519);

MVP

0.061

MPC

0.46

ClinPred

0.11

GERP RS

0.21

Varity_R

0.14

gMVP

0.10

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over