20-56631491-C-A

Variant names:

• chr20-56631491-C-A
• rs1447984930
• NM_003222.4:c.335C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003222.4(TFAP2C):​c.335C>A​(p.Ala112Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,353,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A112V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TFAP2C NM_003222.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07646102).

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.335C>A	p.Ala112Glu	missense	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.335C>A	p.Ala112Glu	missense	Exon 2 of 7	ENSP00000201031.2	Q92754-1
	TFAP2C	ENST00000882953.1		c.335C>A	p.Ala112Glu	missense	Exon 2 of 7	ENSP00000553012.1
	TFAP2C	ENST00000416606.1	TSL:3	c.299C>A	p.Ala100Glu	missense	Exon 2 of 2	ENSP00000390857.1	A2A2R7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 103262 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1353658 Hom.: 0 Cov.: 34 AF XY: 0.00000150 AC XY: 1 AN XY: 666878

African (AFR) AF: 0.00 AC: 0 AN: 28104

American (AMR) AF: 0.00 AC: 0 AN: 28602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22308

East Asian (EAS) AF: 0.00 AC: 0 AN: 33692

South Asian (SAS) AF: 0.00 AC: 0 AN: 72638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4704

European-Non Finnish (NFE) AF: 9.38e-7 AC: 1 AN: 1065810

Other (OTH) AF: 0.00 AC: 0 AN: 56072

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Benign	0.66	T
Sift4G	Benign	0.66	T
Polyphen		0.11	B
Vest4		0.17
MutPred		0.18		Gain of solvent accessibility (P = 0.0456)
MVP		0.54
MPC		1.2
ClinPred		0.14	T
GERP RS		4.7
Varity_R		0.25
gMVP		0.34
Mutation Taster		=86/14	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: rs1447984930; hg19: chr20-55206547;