chr1-35574308-C-T

Variant names:

• chr1-35574308-C-T
• rs1649102920
• NM_178548.4:c.409C>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.409C>T​(p.Pro137Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000023 in 1,305,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: TFAP2E NM_178548.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78
• 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=0.12510642).

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.409C>T	p.Pro137Ser	missense	Exon 2 of 7	NP_848643.2	Q6VUC0
	TFAP2E-AS1	NR_183383.1		n.880+52G>A		intron	N/A
	TFAP2E-AS1	NR_183385.1		n.777+155G>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.409C>T	p.Pro137Ser	missense	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
	TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+52G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000230 AC: 3 AN: 1305982 Hom.: 0 Cov.: 30 AF XY: 0.00000311 AC XY: 2 AN XY: 644118

African (AFR) AF: 0.00 AC: 0 AN: 25578

American (AMR) AF: 0.00 AC: 0 AN: 24384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22194

East Asian (EAS) AF: 0.0000375 AC: 1 AN: 26646

South Asian (SAS) AF: 0.00 AC: 0 AN: 72480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4008

European-Non Finnish (NFE) AF: 9.57e-7 AC: 1 AN: 1044636

Other (OTH) AF: 0.0000186 AC: 1 AN: 53650

GnomAD4 genome Cov.: 33

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	0.25
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.83	L
PhyloP100		3.8
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.17
Sift	Benign	0.71	T
Sift4G	Benign	0.79	T
Polyphen		0.19	B
Vest4		0.15
MutPred		0.21		Loss of glycosylation at T134 (P = 0.0534)
MVP		0.47
MPC		0.81
ClinPred		0.55	D
GERP RS		4.1
Varity_R		0.092
gMVP		0.53
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: rs1649102920; hg19: chr1-36039909;