1-35574356-G-T

Variant names:

• chr1-35574356-G-T
• rs564914229
• NM_178548.4:c.457G>T

Variant summary

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

The NM_178548.4(TFAP2E):​c.457G>T​(p.Ala153Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000775 in 1,290,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A153T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: TFAP2E NM_178548.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 0 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: 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=0.18326882).

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.457G>T	p.Ala153Ser	missense	Exon 2 of 7	NP_848643.2	Q6VUC0
	TFAP2E-AS1	NR_183383.1		n.880+4C>A		splice_region intron	N/A
	TFAP2E-AS1	NR_183385.1		n.777+107C>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.457G>T	p.Ala153Ser	missense	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
	TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+4C>A		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.75e-7 AC: 1 AN: 1290294 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 633940

African (AFR) AF: 0.00 AC: 0 AN: 25434

American (AMR) AF: 0.00 AC: 0 AN: 17344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20190

East Asian (EAS) AF: 0.00 AC: 0 AN: 29130

South Asian (SAS) AF: 0.00 AC: 0 AN: 65952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042568

Other (OTH) AF: 0.0000187 AC: 1 AN: 53494

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	-0.053	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.83	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.013	B
Vest4		0.14
MutPred		0.16		Gain of glycosylation at A153 (P = 0.0067)
MVP		0.76
MPC		0.65
ClinPred		0.44	T
GERP RS		4.3
Varity_R		0.076
gMVP		0.29
Mutation Taster		=88/12	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: rs564914229; hg19: chr1-36039957;