Variant 16-4258152-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_003223.3(TFAP4):c.920C>A(p.Ala307Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,706 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: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TFAP4
NM_003223.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09038019).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TFAP4	NM_003223.3 linkuse as main transcript	c.920C>A	p.Ala307Asp	missense_variant	7/7	ENST00000204517.11	NP_003214.1
TFAP4	XM_047434553.1 linkuse as main transcript	c.1514C>A	p.Ala505Asp	missense_variant	7/7		XP_047290509.1
TFAP4	XM_011522633.4 linkuse as main transcript	c.881C>A	p.Ala294Asp	missense_variant	7/7		XP_011520935.1
TFAP4	XM_011522635.4 linkuse as main transcript	c.740C>A	p.Ala247Asp	missense_variant	7/7		XP_011520937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TFAP4	ENST00000204517.11 linkuse as main transcript	c.920C>A	p.Ala307Asp	missense_variant	7/7	1	NM_003223.3	ENSP00000204517	P1
TFAP4	ENST00000575320.1 linkuse as main transcript	n.5526C>A		non_coding_transcript_exon_variant	5/5	2
TFAP4	ENST00000575672.1 linkuse as main transcript	n.647C>A		non_coding_transcript_exon_variant	1/1
TFAP4	ENST00000574639.1 linkuse as main transcript			downstream_gene_variant		5		ENSP00000461352

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247974

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134436

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000988

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000247

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

May 30, 2024

The c.920C>A (p.A307D) alteration is located in exon 7 (coding exon 7) of the TFAP4 gene. This alteration results from a C to A substitution at nucleotide position 920, causing the alanine (A) at amino acid position 307 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

0.091

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.12

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.090

MetaSVM

Pathogenic

0.91

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.54

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.56

REVEL

Uncertain

0.41

Sift

Uncertain

0.013

Sift4G

Benign

0.54

Polyphen

0.023

Vest4

0.18

MVP

0.35

MPC

0.65

ClinPred

0.14

GERP RS

3.6

Varity_R

0.16

gMVP

0.24

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

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