6-10398543-C-A

Position:

• chr6-10398543-C-A

Variant summary

Our verdict is Benign. Variant got -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 (★★).

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAP2A	NM_001372066.1	c.1194G>T	p.Thr398Thr	synonymous_variant	7/7	ENST00000379613.10	NP_001358995.1
TFAP2A	NM_001042425.3	c.1176G>T	p.Thr392Thr	synonymous_variant	7/7		NP_001035890.1
TFAP2A	NM_001032280.3	c.1170G>T	p.Thr390Thr	synonymous_variant	7/7		NP_001027451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000379613.10	c.1194G>T	p.Thr398Thr	synonymous_variant	7/7	1	NM_001372066.1	ENSP00000368933.5

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

GnomAD3 exomes AF: 0.00367 AC: 923 AN: 251412 Hom.: 18 AF XY: 0.00258 AC XY: 351 AN XY: 135888

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 SAS exome AF: 0.0000980

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

Gnomad4 AFR exome AF: 0.0522

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00253

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

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.00581

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00410 Hom.: 6

Bravo AF: 0.0167

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 21, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.5
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs2230116; hg19: chr6-10398776;