1-35574162-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_178548.4(TFAP2E):​c.263C>T​(p.Ala88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,423,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: TFAP2E NM_178548.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10822776).
• BS2: High AC in GnomAdExome4 at 148 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>T	p.Ala88Val	missense	Exon 2 of 7	NP_848643.2	Q6VUC0
	TFAP2E-AS1	NR_183383.1		n.880+198G>A		intron	N/A
	TFAP2E-AS1	NR_183385.1		n.777+301G>A		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>T	p.Ala88Val	missense	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
	TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+198G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 150050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000543 AC: 4 AN: 73648 AF XY: 0.0000935

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: 0.000111

Gnomad OTH exome AF: 0.000472

GnomAD4 exome AF: 0.000116 AC: 148 AN: 1273410 Hom.: 0 Cov.: 30 AF XY: 0.000111 AC XY: 70 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: 0.00 AC: 0 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: 0.000144 AC: 147 AN: 1021350

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

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 150050 Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1 AN XY: 73224

African (AFR) AF: 0.0000243 AC: 1 AN: 41222

American (AMR) AF: 0.00 AC: 0 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67306

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000212 AC: 1

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	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.78
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.090
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.39	T
Polyphen		0.17	B
Vest4		0.16
MutPred		0.35		Loss of glycosylation at P89 (P = 0.1444)
MVP		0.34
MPC		0.68
ClinPred		0.13	T
GERP RS		1.8
Varity_R		0.12
gMVP		0.39
Mutation Taster		=82/18	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;