6-10398468-G-T

Position:

• chr6-10398468-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001372066.1(TFAP2A):​c.1269C>A​(p.His423Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: TFAP2A NM_001372066.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.14

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37399203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAP2A	NM_001372066.1	c.1269C>A	p.His423Gln	missense_variant	7/7	ENST00000379613.10	NP_001358995.1
TFAP2A	NM_001042425.3	c.1251C>A	p.His417Gln	missense_variant	7/7		NP_001035890.1
TFAP2A	NM_001032280.3	c.1245C>A	p.His415Gln	missense_variant	7/7		NP_001027451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000379613.10	c.1269C>A	p.His423Gln	missense_variant	7/7	1	NM_001372066.1	ENSP00000368933.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Branchiooculofacial syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	.;.;.;D
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D;.;D;D
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Benign	1.9	.;.;.;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.43	T;T;T;T
Sift4G	Benign	0.66	T;T;T;T
Polyphen		0.97	.;.;.;D
Vest4		0.54
MutPred		0.071		.;.;.;Gain of glycosylation at P418 (P = 0.1);
MVP		0.90
ClinPred		0.71	D
GERP RS		5.4
Varity_R		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-10398701; COSMIC: COSV60238751; COSMIC: COSV60238751;