chr3-141952577-G-T

Position:

• chr3-141952577-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001178139.2(TFDP2):​c.1277C>A​(p.Thr426Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,417,254 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TFDP2 NM_001178139.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.21

Genes affected

TFDP2 (HGNC:11751): (transcription factor Dp-2) The gene is a member of the transcription factor DP family. The encoded protein forms heterodimers with the E2F transcription factors resulting in transcriptional activation of cell cycle regulated genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFDP2	NM_001178139.2	c.1277C>A	p.Thr426Asn	missense_variant	13/13	ENST00000489671.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFDP2	ENST00000489671.6	c.1277C>A	p.Thr426Asn	missense_variant	13/13	1	NM_001178139.2	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1417254 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 704256

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: 0.00

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.1277C>A (p.T426N) alteration is located in exon 13 (coding exon 12) of the TFDP2 gene. This alteration results from a C to A substitution at nucleotide position 1277, causing the threonine (T) at amino acid position 426 to be replaced by an asparagine (N). 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	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;.;.;.;.;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;.;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.97	L;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.4	N;.;N;N;N;N;N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;.;D;D;D;D;D
Sift4G	Uncertain	0.052	T;D;D;D;D;D;D
Polyphen		1.0	D;.;D;.;.;D;.
Vest4		0.67
MutPred		0.19		Loss of phosphorylation at T426 (P = 0.019);.;.;.;.;.;.;
MVP		0.13
MPC		1.1
ClinPred		0.84	D
GERP RS		6.0
Varity_R		0.58
gMVP		0.59

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

Other links and lift over

dbSNP: rs377110493; hg19: chr3-141671419;