Variant 6-35475055-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003214.4(TEAD3):c.1297G>A(p.Val433Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,583,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

TEAD3
NM_003214.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

Variant links:

Genes affected

TEAD3 (HGNC:11716): (TEA domain transcription factor 3) This gene product is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which contain the TEA/ATTS DNA-binding domain. It is predominantly expressed in the placenta and is involved in the transactivation of the chorionic somatomammotropin-B gene enhancer. Translation of this protein is initiated at a non-AUG (AUA) start codon. [provided by RefSeq, Jul 2008]

TEAD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14723355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEAD3	NM_003214.4 linkuse as main transcript	c.1297G>A	p.Val433Ile	missense_variant	13/13	ENST00000338863.13	NP_003205.2	Q99594
TEAD3	NM_001395214.1 linkuse as main transcript	c.1297G>A	p.Val433Ile	missense_variant	13/13		NP_001382143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEAD3	ENST00000338863.13 linkuse as main transcript	c.1297G>A	p.Val433Ile	missense_variant	13/13	1	NM_003214.4	ENSP00000345772.8	Q99594A0A1X7SBS4
TEAD3	ENST00000639578.3 linkuse as main transcript	c.1297G>A	p.Val433Ile	missense_variant	13/13	1		ENSP00000492431.3	A0A7P0SNI2
TEAD3	ENST00000402886.9 linkuse as main transcript	n.*698G>A		non_coding_transcript_exon_variant	11/11	1		ENSP00000384577.5	B5MCM0
TEAD3	ENST00000402886.9 linkuse as main transcript	n.*698G>A		3_prime_UTR_variant	11/11	1		ENSP00000384577.5	B5MCM0

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000486

AC:

AN:

205906

Hom.:

AF XY:

0.0000633

AC XY:

AN XY:

110662

show subpopulations

Gnomad AFR exome

AF:

0.0000803

Gnomad AMR exome

AF:

0.0000339

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000650

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000772

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1431116

Hom.:

Cov.:

AF XY:

0.0000381

AC XY:

AN XY:

709198

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.0000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0000367

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000356

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

The c.1297G>A (p.V433I) alteration is located in exon 13 (coding exon 12) of the TEAD3 gene. This alteration results from a G to A substitution at nucleotide position 1297, causing the valine (V) at amino acid position 433 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.77

N;.

REVEL

Benign

0.11

Sift

Benign

0.27

T;.

Sift4G

Benign

0.29

T;.

MutPred

0.34

Gain of methylation at K431 (P = 0.132);Gain of methylation at K431 (P = 0.132);

MVP

0.10

ClinPred

0.039

GERP RS

5.2

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over