X-133217869-G-A

Variant names:

• chrX-133217869-G-A
• rs984408004
• NM_016521.3:c.391C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016521.3(TFDP3):​c.391C>T​(p.Gln131*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,966 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: TFDP3 NM_016521.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.391C>T	p.Gln131*	stop_gained	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.391C>T	p.Gln131*	stop_gained	Exon 1 of 1	ENSP00000385461.1	Q5H9I0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097966 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 363386

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54141

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4060

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842027

Other (OTH) AF: 0.00 AC: 0 AN: 46068

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Benign	0.94
FATHMM_MKL	Benign	0.28	N
PhyloP100		3.2
Vest4		0.024
GERP RS		-0.45
PromoterAI		-0.14	Neutral
Mutation Taster		=163/37	polymorphism

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

Other links and lift over

dbSNP: rs984408004; hg19: chrX-132351897;