6-50823581-T-A

Position:

• chr6-50823581-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003221.4(TFAP2B):​c.256T>A​(p.Tyr86Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TFAP2B NM_003221.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.20

Genes affected

TFAP2B (HGNC:11743): (transcription factor AP-2 beta) This gene encodes a member of the AP-2 family of transcription factors. AP-2 proteins form homo- or hetero-dimers with other AP-2 family members and bind specific DNA sequences. They are thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development. Specific AP-2 family members differ in their expression patterns and binding affinity for different promoters. This protein functions as both a transcriptional activator and repressor. Mutations in this gene result in autosomal dominant Char syndrome, suggesting that this gene functions in the differentiation of neural crest cell derivatives. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAP2B	NM_003221.4	c.256T>A	p.Tyr86Asn	missense_variant	2/7	ENST00000393655.4	NP_003212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2B	ENST00000393655.4	c.256T>A	p.Tyr86Asn	missense_variant	2/7	1	NM_003221.4	ENSP00000377265	P1
TFAP2B	ENST00000344788.7	c.250T>A	p.Tyr84Asn	missense_variant	3/4	3		ENSP00000342252
TFAP2B	ENST00000489228.1	n.551T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jul 24, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.84	.;D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Uncertain	2.8	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.031	D;T
Polyphen		1.0	.;D
Vest4		0.90
MutPred		0.45		.;Loss of phosphorylation at Y86 (P = 0.0015);
MVP		0.87
MPC		1.2
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.77
gMVP		0.63

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: chr6-50791294;