Variant 16-4260178-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_003223.3(TFAP4):c.734C>T(p.Ser245Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000865 in 1,594,686 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: 𝑓 0.00022 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

TFAP4
NM_003223.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.15

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=0.095204204).

BS2

High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TFAP4	NM_003223.3 linkuse as main transcript	c.734C>T	p.Ser245Phe	missense_variant	6/7	ENST00000204517.11	NP_003214.1
TFAP4	XM_047434553.1 linkuse as main transcript	c.1328C>T	p.Ser443Phe	missense_variant	6/7		XP_047290509.1
TFAP4	XM_011522633.4 linkuse as main transcript	c.695C>T	p.Ser232Phe	missense_variant	6/7		XP_011520935.1
TFAP4	XM_011522635.4 linkuse as main transcript	c.554C>T	p.Ser185Phe	missense_variant	6/7		XP_011520937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TFAP4	ENST00000204517.11 linkuse as main transcript	c.734C>T	p.Ser245Phe	missense_variant	6/7	1	NM_003223.3	ENSP00000204517	P1
TFAP4	ENST00000575320.1 linkuse as main transcript	n.5340C>T		non_coding_transcript_exon_variant	4/5	2
TFAP4	ENST00000574639.1 linkuse as main transcript	c.*163C>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	5		ENSP00000461352

Frequencies

GnomAD3 genomes

AF:

0.000218

AC:

AN:

151606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000181

AC:

AN:

231874

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

125748

show subpopulations

Gnomad AFR exome

AF:

0.000644

Gnomad AMR exome

AF:

0.000719

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000750

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.0000728

AC:

105

AN:

1442962

Hom.:

Cov.:

AF XY:

0.0000739

AC XY:

AN XY:

717658

show subpopulations

Gnomad4 AFR exome

AF:

0.000371

Gnomad4 AMR exome

AF:

0.000564

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000434

Gnomad4 OTH exome

AF:

0.000302

GnomAD4 genome

AF:

0.000218

AC:

AN:

151724

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.000531

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000885

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.000295

ExAC

AF:

0.000189

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

Aug 13, 2021

The c.734C>T (p.S245F) alteration is located in exon 6 (coding exon 6) of the TFAP4 gene. This alteration results from a C to T substitution at nucleotide position 734, causing the serine (S) at amino acid position 245 to be replaced by a phenylalanine (F). 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

0.19

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.095

MetaSVM

Pathogenic

0.98

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.49

Sift

Benign

0.049

Sift4G

Benign

0.10

Polyphen

0.83

Vest4

0.49

MVP

0.47

MPC

0.47

ClinPred

0.044

GERP RS

4.8

Varity_R

0.17

gMVP

0.33

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