Variant 13-113637877-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007111.5(TFDP1):c.1066G>A(p.Gly356Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TFDP1
NM_007111.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92

Variant links:

Genes affected

TFDP1 (HGNC:11749): (transcription factor Dp-1) This gene encodes a member of a family of transcription factors that heterodimerize with E2F proteins to enhance their DNA-binding activity and promote transcription from E2F target genes. The encoded protein functions as part of this complex to control the transcriptional activity of numerous genes involved in cell cycle progression from G1 to S phase. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 1, 15, and X.[provided by RefSeq, Jan 2009]

TFDP1 links:

TFDP1 (HGNC:):

TFDP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24669966).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFDP1	NM_007111.5 linkuse as main transcript	c.1066G>A	p.Gly356Ser	missense_variant	11/12	ENST00000375370.10	NP_009042.1	Q14186-1A0A024RDY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TFDP1	ENST00000375370.10 linkuse as main transcript	c.1066G>A	p.Gly356Ser	missense_variant	11/12	1	NM_007111.5	ENSP00000364519.4	Q14186-1
TFDP1	ENST00000494812.1 linkuse as main transcript	n.152G>A		non_coding_transcript_exon_variant	2/3	3
TFDP1	ENST00000544902.5 linkuse as main transcript	n.*782G>A		non_coding_transcript_exon_variant	10/11	2		ENSP00000438450.2	F5H452
TFDP1	ENST00000544902.5 linkuse as main transcript	n.*782G>A		3_prime_UTR_variant	10/11	2		ENSP00000438450.2	F5H452

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251462

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461416

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727008

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000829

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.1066G>A (p.G356S) alteration is located in exon 11 (coding exon 10) of the TFDP1 gene. This alteration results from a G to A substitution at nucleotide position 1066, causing the glycine (G) at amino acid position 356 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

Eigen

Benign

0.0078

Eigen_PC

Benign

0.093

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.022

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.0

REVEL

Benign

0.14

Sift

Benign

0.11

Sift4G

Benign

0.21

Polyphen

0.46

Vest4

0.50

MutPred

0.27

Gain of catalytic residue at S352 (P = 0.007);

MVP

0.11

MPC

0.43

ClinPred

0.56

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over