Genetic Variant TFAP2C:p.Ser41Ser (chr20-56631279-C-T) – ACMG Classification: Benign (-17 pts)

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

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]

TFAP2C links:

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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
TFAP2C	NM_003222.4 link	c.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
TFAP2C	ENST00000201031.3 link	c.123C>T	p.Ser41Ser	synonymous_variant	Exon 2 of 7	1	NM_003222.4	ENSP00000201031.2		Q92754-1
TFAP2C	ENST00000416606.1 link	c.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.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00272

Asia WGS

AF:

0.000577

AC:

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

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.

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