6-10398329-G-T

Variant names:

• chr6-10398329-G-T
• rs10456013
• ENST00000488193.7:n.*899C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000488193.7(TFAP2A):​n.*899C>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.05 in 1,606,400 control chromosomes in the GnomAD database, including 2,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (133 hom., cov: 29)
  • Exomes 𝑓: 0.052 (2378 hom.)
• Consequence: TFAP2A ENST00000488193.7 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.43
• Publications: 3 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: Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-10398329-G-T is Benign according to our data. Variant chr6-10398329-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1203480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488193.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	NM_001372066.1	MANE Select	c.*88C>A		3_prime_UTR	Exon 7 of 7	NP_001358995.1
	TFAP2A	NM_001042425.3		c.*88C>A		3_prime_UTR	Exon 7 of 7	NP_001035890.1
	TFAP2A	NM_001032280.3		c.*88C>A		3_prime_UTR	Exon 7 of 7	NP_001027451.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000488193.7	TSL:1	n.*899C>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000419823.3
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.*88C>A		3_prime_UTR	Exon 7 of 7	ENSP00000368933.5
	TFAP2A	ENST00000379608.9	TSL:1	c.*88C>A		3_prime_UTR	Exon 7 of 7	ENSP00000368928.3

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4918 AN: 150602 Hom.: 133 Cov.: 29

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0518 AC: 75447 AN: 1455684 Hom.: 2378 Cov.: 36 AF XY: 0.0505 AC XY: 36552 AN XY: 723932

African (AFR) AF: 0.00836 AC: 279 AN: 33386

American (AMR) AF: 0.0135 AC: 603 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 462 AN: 25956

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39646

South Asian (SAS) AF: 0.0157 AC: 1350 AN: 85902

European-Finnish (FIN) AF: 0.0262 AC: 1358 AN: 51852

Middle Eastern (MID) AF: 0.00471 AC: 21 AN: 4458

European-Non Finnish (NFE) AF: 0.0619 AC: 68656 AN: 1109806

Other (OTH) AF: 0.0452 AC: 2715 AN: 60042

GnomAD4 genome AF: 0.0326 AC: 4918 AN: 150716 Hom.: 133 Cov.: 29 AF XY: 0.0308 AC XY: 2262 AN XY: 73554

African (AFR) AF: 0.0111 AC: 455 AN: 40958

American (AMR) AF: 0.0230 AC: 348 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3462

East Asian (EAS) AF: 0.000593 AC: 3 AN: 5062

South Asian (SAS) AF: 0.0124 AC: 59 AN: 4762

European-Finnish (FIN) AF: 0.0229 AC: 237 AN: 10360

Middle Eastern (MID) AF: 0.0172 AC: 5 AN: 290

European-Non Finnish (NFE) AF: 0.0542 AC: 3669 AN: 67726

Other (OTH) AF: 0.0284 AC: 59 AN: 2080

Alfa AF: 0.0146 Hom.: 2

Bravo AF: 0.0313

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 17, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		6.4
Mutation Taster		=100/0	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: rs10456013; hg19: chr6-10398562;