rs750830375

Variant names:

• chr20-56631641-C-A
• rs750830375
• NM_003222.4:c.485C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-56631641-C-A
• chr20-56631641-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003222.4(TFAP2C):​c.485C>A​(p.Ala162Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A162V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TFAP2C NM_003222.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.222
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31682116).

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.485C>A	p.Ala162Asp	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.485C>A	p.Ala162Asp	missense	Exon 2 of 7	ENSP00000201031.2	Q92754-1
	TFAP2C	ENST00000882953.1		c.485C>A	p.Ala162Asp	missense	Exon 2 of 7	ENSP00000553012.1
	TFAP2C	ENST00000416606.1	TSL:3	c.*94C>A		downstream_gene	N/A	ENSP00000390857.1	A2A2R7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426900 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 708144

African (AFR) AF: 0.00 AC: 0 AN: 32520

American (AMR) AF: 0.00 AC: 0 AN: 41710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25020

East Asian (EAS) AF: 0.00 AC: 0 AN: 38530

South Asian (SAS) AF: 0.00 AC: 0 AN: 81846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100352

Other (OTH) AF: 0.00 AC: 0 AN: 59186

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.22
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.22
Sift	Uncertain	0.012	D
Sift4G	Benign	0.40	T
Polyphen		0.97	D
Vest4		0.56
MutPred		0.39		Gain of loop (P = 0.0435)
MVP		0.36
MPC		1.8
ClinPred		0.90	D
GERP RS		3.4
Varity_R		0.30
gMVP		0.49
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs750830375; hg19: chr20-55206697;