X-133217050-C-A

Variant names:

• chrX-133217050-C-A
• rs2068013713
• NM_016521.3:c.1210G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016521.3(TFDP3):​c.1210G>T​(p.Asp404Tyr) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: TFDP3 NM_016521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067469984).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016521.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFDP3	NM_016521.3	MANE Select	c.1210G>T	p.Asp404Tyr	missense	Exon 1 of 1	NP_057605.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFDP3	ENST00000310125.5	TSL:6 MANE Select	c.1210G>T	p.Asp404Tyr	missense	Exon 1 of 1	ENSP00000385461.1	Q5H9I0

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.22e-7 AC: 1 AN: 1084740 Hom.: 0 Cov.: 32 AF XY: 0.00000283 AC XY: 1 AN XY: 353182

African (AFR) AF: 0.0000383 AC: 1 AN: 26123

American (AMR) AF: 0.00 AC: 0 AN: 34155

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18841

East Asian (EAS) AF: 0.00 AC: 0 AN: 29918

South Asian (SAS) AF: 0.00 AC: 0 AN: 52423

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4062

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833432

Other (OTH) AF: 0.00 AC: 0 AN: 45472

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.31
DEOGEN2	Benign	0.0042	T
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		3.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.12
Sift	Benign	0.39	T
Sift4G	Pathogenic	0.0010	D
Polyphen		0.0	B
Vest4		0.18
MutPred		0.16		Gain of phosphorylation at D404 (P = 0.0079)
MVP		0.085
MPC		0.25
ClinPred		0.11	T
GERP RS		-0.69
Varity_R		0.096
gMVP		0.036
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2068013713; hg19: chrX-132351078; COSMIC: COSV59537053;