Variant 16-4260482-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000204517.11(TFAP4):c.639G>T(p.Glu213Asp) 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. 13/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TFAP4
ENST00000204517.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

TFAP4 (HGNC:11745): (transcription factor AP-4) Transcription factors of the basic helix-loop-helix-zipper (bHLH-ZIP) family contain a basic domain, which is used for DNA binding, and HLH and ZIP domains, which are used for oligomerization. Transcription factor AP4 activates both viral and cellular genes by binding to the symmetrical DNA sequence CAGCTG (Mermod et al., 1988 [PubMed 2833704]; Hu et al., 1990 [PubMed 2123466]).[supplied by OMIM, Jul 2009]

TFAP4 links:

TFAP4 (HGNC:):

TFAP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118887246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAP4	NM_003223.3 linkuse as main transcript	c.639G>T	p.Glu213Asp	missense_variant	5/7	ENST00000204517.11	NP_003214.1	Q01664
TFAP4	XM_047434553.1 linkuse as main transcript	c.1233G>T	p.Glu411Asp	missense_variant	5/7		XP_047290509.1
TFAP4	XM_011522633.4 linkuse as main transcript	c.600G>T	p.Glu200Asp	missense_variant	5/7		XP_011520935.1
TFAP4	XM_011522635.4 linkuse as main transcript	c.459G>T	p.Glu153Asp	missense_variant	5/7		XP_011520937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP4	ENST00000204517.11 linkuse as main transcript	c.639G>T	p.Glu213Asp	missense_variant	5/7	1	NM_003223.3	ENSP00000204517.6		Q01664

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721498

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:

0.00

GnomAD4 genome

Cov.:

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

Apr 15, 2024

The c.639G>T (p.E213D) alteration is located in exon 5 (coding exon 5) of the TFAP4 gene. This alteration results from a G to T substitution at nucleotide position 639, causing the glutamic acid (E) at amino acid position 213 to be replaced by an aspartic acid (D). 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

0.094

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.024

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

M_CAP

Benign

0.029

MetaRNN

Benign

0.12

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

0.060

MutationTaster

Benign

0.92

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.79

REVEL

Uncertain

0.35

Sift

Benign

0.16

Sift4G

Benign

0.43

Polyphen

0.0010

Vest4

0.13

MutPred

0.10

Gain of MoRF binding (P = 0.1786);

MVP

0.35

MPC

0.39

ClinPred

0.37

GERP RS

4.8

Varity_R

0.17

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over