rs2230116

Variant names:

• chr6-10398543-C-A
• rs2230116
• NM_001372066.1:c.1194G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-10398543-C-A
• chr6-10398543-C-T
• chr6-10398543-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001372066.1(TFAP2A):​c.1194G>T​(p.Thr398Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,614,180 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T398T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.015 (60 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (51 hom.)
• Consequence: TFAP2A NM_001372066.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.63
• Publications: 4 publications found

Genes affected

TFAP2A (HGNC:11742): (transcription factor AP-2 alpha) The protein encoded by this gene is a transcription factor that binds the consensus sequence 5'-GCCNNNGGC-3'. The encoded protein functions as either a homodimer or as a heterodimer with similar family members. This protein activates the transcription of some genes while inhibiting the transcription of others. Defects in this gene are a cause of branchiooculofacial syndrome (BOFS). Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

TFAP2A Gene-Disease associations (from GenCC):

• branchiooculofacial syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 6-10398543-C-A is Benign according to our data. Variant chr6-10398543-C-A is described in ClinVar as Benign. ClinVar VariationId is 780594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.63 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372066.1. 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
	TFAP2A	NM_001372066.1	MANE Select	c.1194G>T	p.Thr398Thr	synonymous	Exon 7 of 7	NP_001358995.1	A0A6E1XE14
	TFAP2A	NM_001042425.3		c.1176G>T	p.Thr392Thr	synonymous	Exon 7 of 7	NP_001035890.1	P05549-6
	TFAP2A	NM_001032280.3		c.1170G>T	p.Thr390Thr	synonymous	Exon 7 of 7	NP_001027451.1	P05549-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.1194G>T	p.Thr398Thr	synonymous	Exon 7 of 7	ENSP00000368933.5	A0A6E1XE14
	TFAP2A	ENST00000379608.9	TSL:1	c.1170G>T	p.Thr390Thr	synonymous	Exon 7 of 7	ENSP00000368928.3	P05549-5
	TFAP2A	ENST00000488193.7	TSL:1	n.*685G>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000419823.3	F8WEX2

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2226 AN: 152172 Hom.: 60 Cov.: 33

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00367 AC: 923 AN: 251412 AF XY: 0.00258

Gnomad AFR exome AF: 0.0509

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.00141 AC: 2058 AN: 1461890 Hom.: 51 Cov.: 37 AF XY: 0.00117 AC XY: 853 AN XY: 727246

African (AFR) AF: 0.0522 AC: 1747 AN: 33480

American (AMR) AF: 0.00273 AC: 122 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1112010

Other (OTH) AF: 0.00253 AC: 153 AN: 60396

GnomAD4 genome AF: 0.0146 AC: 2225 AN: 152290 Hom.: 60 Cov.: 33 AF XY: 0.0140 AC XY: 1045 AN XY: 74474

African (AFR) AF: 0.0505 AC: 2100 AN: 41554

American (AMR) AF: 0.00581 AC: 89 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68016

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00491 Hom.: 13

Bravo AF: 0.0167

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.5
DANN	Benign	0.86
PhyloP100		-2.6
Mutation Taster		=99/1	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: rs2230116; hg19: chr6-10398776;