chr1-35574267-C-T

Variant names:

• chr1-35574267-C-T
• rs1355555781
• NM_178548.4:c.368C>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.368C>T​(p.Ala123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 150,316 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TFAP2E NM_178548.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• 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=0.227433).

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.368C>T	p.Ala123Val	missense	Exon 2 of 7	NP_848643.2	Q6VUC0
	TFAP2E-AS1	NR_183383.1		n.880+93G>A		intron	N/A
	TFAP2E-AS1	NR_183385.1		n.777+196G>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.368C>T	p.Ala123Val	missense	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
	TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+93G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 AN: 150316 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1230628 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 606872

African (AFR) AF: 0.00 AC: 0 AN: 23274

American (AMR) AF: 0.00 AC: 0 AN: 19078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19462

East Asian (EAS) AF: 0.00 AC: 0 AN: 20754

South Asian (SAS) AF: 0.00 AC: 0 AN: 67974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3444

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 997538

Other (OTH) AF: 0.00 AC: 0 AN: 48668

GnomAD4 genome AF: 0.00000665 AC: 1 AN: 150316 Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1 AN XY: 73362

African (AFR) AF: 0.00 AC: 0 AN: 41222

American (AMR) AF: 0.0000663 AC: 1 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9770

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67476

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.23
Sift	Benign	0.18	T
Sift4G	Benign	0.14	T
Polyphen		0.020	B
Vest4		0.14
MutPred		0.13		Loss of methylation at R122 (P = 0.1207)
MVP		0.64
MPC		0.67
ClinPred		0.80	D
GERP RS		3.8
Varity_R		0.17
gMVP		0.45
Mutation Taster		=70/30	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: rs1355555781; hg19: chr1-36039868;