Variant 20-56631491-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003222.4(TFAP2C):c.335C>T(p.Ala112Val) 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. 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TFAP2C
NM_003222.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

TFAP2C (HGNC:11744): (transcription factor AP-2 gamma) The protein encoded by this gene is a sequence-specific DNA-binding transcription factor involved in the activation of several developmental genes. The encoded protein can act as either a homodimer or heterodimer with other family members and is induced during retinoic acid-mediated differentiation. It plays a role in the development of the eyes, face, body wall, limbs, and neural tube. [provided by RefSeq, Jul 2008]

TFAP2C links:

Genome browser will be placed here

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=0.0833568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAP2C	NM_003222.4 linkuse as main transcript	c.335C>T	p.Ala112Val	missense_variant	2/7	ENST00000201031.3	NP_003213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2C	ENST00000201031.3 linkuse as main transcript	c.335C>T	p.Ala112Val	missense_variant	2/7	1	NM_003222.4	ENSP00000201031	P1	Q92754-1
TFAP2C	ENST00000416606.1 linkuse as main transcript	c.299C>T	p.Ala100Val	missense_variant	2/2	3		ENSP00000390857

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1353654

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666876

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

Mar 11, 2022

The c.335C>T (p.A112V) alteration is located in exon 2 (coding exon 2) of the TFAP2C gene. This alteration results from a C to T substitution at nucleotide position 335, causing the alanine (A) at amino acid position 112 to be replaced by a valine (V). 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

0.081

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.083

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.15

Sift

Benign

0.62

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.10

B;.

Vest4

0.30

MutPred

0.14

Loss of glycosylation at S108 (P = 0.1213);.;

MVP

0.61

MPC

0.95

ClinPred

0.21

GERP RS

4.7

Varity_R

0.16

gMVP

0.32

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