NM_003222.4:c.123C>T

Variant names:

• chr20-56631279-C-T
• rs144019270
• NM_003222.4:c.123C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003222.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2C	NM_003222.4	MANE Select	c.123C>T	p.Ser41Ser	synonymous	Exon 2 of 7	NP_003213.1	Q92754-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2C	ENST00000201031.3	TSL:1 MANE Select	c.123C>T	p.Ser41Ser	synonymous	Exon 2 of 7	ENSP00000201031.2	Q92754-1
	TFAP2C	ENST00000882953.1		c.123C>T	p.Ser41Ser	synonymous	Exon 2 of 7	ENSP00000553012.1
	TFAP2C	ENST00000416606.1	TSL:3	c.87C>T	p.Ser29Ser	synonymous	Exon 2 of 2	ENSP00000390857.1	A2A2R7

Frequencies

GnomAD3 genomes AF: 0.00284 AC: 432 AN: 152018 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.00260 AC: 623 AN: 239972 AF XY: 0.00258

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 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

African (AFR) AF: 0.000826 AC: 27 AN: 32684

American (AMR) AF: 0.00225 AC: 98 AN: 43504

Ashkenazi Jewish (ASJ) AF: 0.000387 AC: 10 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 38806

South Asian (SAS) AF: 0.000130 AC: 11 AN: 84556

European-Finnish (FIN) AF: 0.00805 AC: 425 AN: 52780

Middle Eastern (MID) AF: 0.00244 AC: 14 AN: 5726

European-Non Finnish (NFE) AF: 0.00416 AC: 4606 AN: 1108348

Other (OTH) AF: 0.00390 AC: 234 AN: 60024

GnomAD4 genome AF: 0.00284 AC: 432 AN: 152136 Hom.: 1 Cov.: 32 AF XY: 0.00289 AC XY: 215 AN XY: 74372

African (AFR) AF: 0.000819 AC: 34 AN: 41514

American (AMR) AF: 0.00373 AC: 57 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00791 AC: 84 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00368 AC: 250 AN: 67956

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00303 Hom.: 1

Bravo AF: 0.00272

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		1.7
Mutation Taster		=287/13	polymorphism

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

Other links and lift over

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