rs564914229

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-35574356-G-A
• chr1-35574356-G-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.457G>A​(p.Ala153Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000104 in 1,442,540 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: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: TFAP2E NM_178548.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2230247).
• BS2: High AC in GnomAd4 at 10 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.457G>A	p.Ala153Thr	missense	Exon 2 of 7	NP_848643.2	Q6VUC0
	TFAP2E-AS1	NR_183383.1		n.880+4C>T		splice_region intron	N/A
	TFAP2E-AS1	NR_183385.1		n.777+107C>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.457G>A	p.Ala153Thr	missense	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
	TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+4C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000415 AC: 2 AN: 48222 AF XY: 0.0000708

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000466

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000388 AC: 5 AN: 1290292 Hom.: 0 Cov.: 30 AF XY: 0.00000473 AC XY: 3 AN XY: 633938

African (AFR) AF: 0.0000786 AC: 2 AN: 25434

American (AMR) AF: 0.0000577 AC: 1 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: 65950

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: 0.00000192 AC: 2 AN: 1042568

Other (OTH) AF: 0.00 AC: 0 AN: 53494

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74450

African (AFR) AF: 0.000241 AC: 10 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

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	0.082
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.43	D
MutationAssessor	Benign	1.0	L
PhyloP100		3.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.18	N
REVEL	Uncertain	0.31
Sift	Benign	0.25	T
Sift4G	Benign	0.34	T
Polyphen		0.52	P
Vest4		0.17
MutPred		0.20		Gain of glycosylation at A153 (P = 0.0525)
MVP		0.75
MPC		0.67
ClinPred		0.19	T
GERP RS		4.3
Varity_R		0.067
gMVP		0.31
Mutation Taster		=79/21	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;