Variant 16-4258082-C-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_003223.3(TFAP4):c.990G>T(p.Glu330Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000048 ( 0 hom. )

Consequence

TFAP4
NM_003223.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.182

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.071695626).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TFAP4	NM_003223.3 linkuse as main transcript	c.990G>T	p.Glu330Asp	missense_variant	7/7	ENST00000204517.11	NP_003214.1
TFAP4	XM_047434553.1 linkuse as main transcript	c.1584G>T	p.Glu528Asp	missense_variant	7/7		XP_047290509.1
TFAP4	XM_011522633.4 linkuse as main transcript	c.951G>T	p.Glu317Asp	missense_variant	7/7		XP_011520935.1
TFAP4	XM_011522635.4 linkuse as main transcript	c.810G>T	p.Glu270Asp	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.990G>T	p.Glu330Asp	missense_variant	7/7	1	NM_003223.3	ENSP00000204517	P1
TFAP4	ENST00000575320.1 linkuse as main transcript	n.5596G>T		non_coding_transcript_exon_variant	5/5	2
TFAP4	ENST00000575672.1 linkuse as main transcript	n.717G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245698

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133608

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000914

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460762

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726692

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

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

Mar 06, 2023

The c.990G>T (p.E330D) alteration is located in exon 7 (coding exon 7) of the TFAP4 gene. This alteration results from a G to T substitution at nucleotide position 990, causing the glutamic acid (E) at amino acid position 330 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

0.056

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.095

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.70

M_CAP

Benign

0.074

MetaRNN

Benign

0.072

MetaSVM

Uncertain

0.051

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.98

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.86

REVEL

Uncertain

0.37

Sift

Benign

0.32

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.040

MutPred

0.093

Gain of helix (P = 0.1736);

MVP

0.46

MPC

0.39

ClinPred

0.10

GERP RS

2.5

Varity_R

0.034

gMVP

0.035

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