1-35574162-C-A

Variant names:

• chr1-35574162-C-A
• rs768908023
• NM_178548.4:c.263C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_178548.4(TFAP2E):​c.263C>A​(p.Ala88Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000432 in 1,273,410 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. A88P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: TFAP2E NM_178548.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779
• Publications: 1 publications found

Genes affected

TFAP2E (HGNC:30774): (transcription factor AP-2 epsilon) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in anatomical structure development; regulation of cell population proliferation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TFAP2E-AS1 (HGNC:41274): (TFAP2E antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023323596).
• BS2: High AC in GnomAdExome4 at 55 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178548.4. 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
	TFAP2E	NM_178548.4	MANE Select	c.263C>A	p.Ala88Glu	missense	Exon 2 of 7	NP_848643.2	Q6VUC0
	TFAP2E-AS1	NR_183383.1		n.880+198G>T		intron	N/A
	TFAP2E-AS1	NR_183385.1		n.777+301G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2E	ENST00000373235.4	TSL:1 MANE Select	c.263C>A	p.Ala88Glu	missense	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
	TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+198G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000231 AC: 17 AN: 73648 AF XY: 0.000304

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: 0.0000432 AC: 55 AN: 1273410 Hom.: 0 Cov.: 30 AF XY: 0.0000652 AC XY: 41 AN XY: 628370

African (AFR) AF: 0.00 AC: 0 AN: 24542

American (AMR) AF: 0.00 AC: 0 AN: 24012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20784

East Asian (EAS) AF: 0.00 AC: 0 AN: 23662

South Asian (SAS) AF: 0.000745 AC: 54 AN: 72488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3642

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1021350

Other (OTH) AF: 0.0000196 AC: 1 AN: 51100

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.000254 AC: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.78
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.33	N
REVEL	Benign	0.083
Sift	Uncertain	0.011	D
Sift4G	Benign	0.22	T
Polyphen		0.31	B
Vest4		0.10
MutPred		0.32		Loss of glycosylation at P93 (P = 0.175)
MVP		0.27
MPC		0.96
ClinPred		0.11	T
GERP RS		1.8
Varity_R		0.16
gMVP		0.44
Mutation Taster		=83/17	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: rs768908023; hg19: chr1-36039763;