3-141959685-C-A

Position:

• chr3-141959685-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001178139.2(TFDP2):​c.1040G>T​(p.Gly347Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: TFDP2 NM_001178139.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34269452).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFDP2	NM_001178139.2	c.1040G>T	p.Gly347Val	missense_variant	11/13	ENST00000489671.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFDP2	ENST00000489671.6	c.1040G>T	p.Gly347Val	missense_variant	11/13	1	NM_001178139.2	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727202

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: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

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

Mar 19, 2024

The c.1040G>T (p.G347V) alteration is located in exon 11 (coding exon 10) of the TFDP2 gene. This alteration results from a G to T substitution at nucleotide position 1040, causing the glycine (G) at amino acid position 347 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.;.;.;.;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.91	D;D;.;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.34	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.071	T;D;T;T;T;T;T
Sift4G	Uncertain	0.038	D;D;T;T;T;T;T
Polyphen		0.88	P;.;P;.;.;P;.
Vest4		0.39
MutPred		0.34		Loss of catalytic residue at I349 (P = 0.0714);.;.;.;.;.;.;
MVP		0.043
MPC		0.61
ClinPred		0.83	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.50

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: rs775539741; hg19: chr3-141678527;