1-35574229-C-T

Variant names:

• chr1-35574229-C-T
• rs1255047638
• NM_178548.4:c.330C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_178548.4(TFAP2E):​c.330C>T​(p.His110His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000673 in 148,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TFAP2E NM_178548.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.599 with no splicing effect.

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.330C>T	p.His110His	synonymous	Exon 2 of 7	NP_848643.2	Q6VUC0
	TFAP2E-AS1	NR_183383.1		n.880+131G>A		intron	N/A
	TFAP2E-AS1	NR_183385.1		n.777+234G>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.330C>T	p.His110His	synonymous	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
	TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+131G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000673 AC: 1 AN: 148686 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1101904 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 537016

African (AFR) AF: 0.00 AC: 0 AN: 20050

American (AMR) AF: 0.00 AC: 0 AN: 7410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12532

East Asian (EAS) AF: 0.00 AC: 0 AN: 17604

South Asian (SAS) AF: 0.00 AC: 0 AN: 47300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 927648

Other (OTH) AF: 0.00 AC: 0 AN: 41720

GnomAD4 genome AF: 0.00000673 AC: 1 AN: 148686 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72476

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41080

American (AMR) AF: 0.00 AC: 0 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9182

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

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66776

Other (OTH) AF: 0.00 AC: 0 AN: 2046

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		0.60
Mutation Taster		=95/5	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: rs1255047638; hg19: chr1-36039830;