20-56631279-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003222.4(TFAP2C):​c.123C>T​(p.Ser41Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00365 in 1,604,426 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0037 ( 11 hom. )

Consequence

TFAP2C
NM_003222.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.65
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 20-56631279-C-T is Benign according to our data. Variant chr20-56631279-C-T is described in ClinVar as [Benign]. Clinvar id is 777549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.65 with no splicing effect.
BS2
High AC in GnomAd4 at 432 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFAP2CNM_003222.4 linkc.123C>T p.Ser41Ser synonymous_variant Exon 2 of 7 ENST00000201031.3 NP_003213.1 Q92754-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TFAP2CENST00000201031.3 linkc.123C>T p.Ser41Ser synonymous_variant Exon 2 of 7 1 NM_003222.4 ENSP00000201031.2 Q92754-1
TFAP2CENST00000416606.1 linkc.87C>T p.Ser29Ser synonymous_variant Exon 2 of 2 3 ENSP00000390857.1 A2A2R7

Frequencies

GnomAD3 genomes
AF:
0.00284
AC:
432
AN:
152018
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000821
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00373
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00791
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00368
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00260
AC:
623
AN:
239972
Hom.:
1
AF XY:
0.00258
AC XY:
336
AN XY:
130268
show subpopulations
Gnomad AFR exome
AF:
0.000595
Gnomad AMR exome
AF:
0.00194
Gnomad ASJ exome
AF:
0.000206
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000346
Gnomad FIN exome
AF:
0.00748
Gnomad NFE exome
AF:
0.00340
Gnomad OTH exome
AF:
0.00278
GnomAD4 exome
AF:
0.00374
AC:
5425
AN:
1452290
Hom.:
11
Cov.:
34
AF XY:
0.00354
AC XY:
2554
AN XY:
722320
show subpopulations
Gnomad4 AFR exome
AF:
0.000826
Gnomad4 AMR exome
AF:
0.00225
Gnomad4 ASJ exome
AF:
0.000387
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000130
Gnomad4 FIN exome
AF:
0.00805
Gnomad4 NFE exome
AF:
0.00416
Gnomad4 OTH exome
AF:
0.00390
GnomAD4 genome
AF:
0.00284
AC:
432
AN:
152136
Hom.:
1
Cov.:
32
AF XY:
0.00289
AC XY:
215
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.000819
Gnomad4 AMR
AF:
0.00373
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00791
Gnomad4 NFE
AF:
0.00368
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.00303
Hom.:
1
Bravo
AF:
0.00272
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
12
DANN
Benign
0.86

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.

Other links and lift over

dbSNP: rs144019270; hg19: chr20-55206335; COSMIC: COSV99571426; API