Variant chr12-3021923-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003213.4(TEAD4):c.803G>T(p.Arg268Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000502 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

TEAD4
NM_003213.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

Variant links:

Genes affected

TEAD4 (HGNC:11717): (TEA domain transcription factor 4) 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 preferentially expressed in the skeletal muscle, and binds to the M-CAT regulatory element found in promoters of muscle-specific genes to direct their gene expression. Alternatively spliced transcripts encoding distinct isoforms, some of which are translated through the use of a non-AUG (UUG) initiation codon, have been described for this gene. [provided by RefSeq, Jul 2008]

TEAD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TEAD4	NM_003213.4 linkuse as main transcript	c.803G>T	p.Arg268Leu	missense_variant	10/13	ENST00000359864.8
TEAD4	NM_201441.3 linkuse as main transcript	c.674G>T	p.Arg225Leu	missense_variant	9/12
TEAD4	NM_201443.3 linkuse as main transcript	c.416G>T	p.Arg139Leu	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEAD4	ENST00000359864.8 linkuse as main transcript	c.803G>T	p.Arg268Leu	missense_variant	10/13	1	NM_003213.4	P1	Q15561-1
TEAD4	ENST00000358409.7 linkuse as main transcript	c.674G>T	p.Arg225Leu	missense_variant	9/12	1			Q15561-3
TEAD4	ENST00000397122.6 linkuse as main transcript	c.416G>T	p.Arg139Leu	missense_variant	8/11	1			Q15561-2
TEAD4	ENST00000544666.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251490

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000527

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000638

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00000824

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

Jan 30, 2024

The c.803G>T (p.R268L) alteration is located in exon 10 (coding exon 8) of the TEAD4 gene. This alteration results from a G to T substitution at nucleotide position 803, causing the arginine (R) at amino acid position 268 to be replaced by a leucine (L). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;D;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.037

D;D;D

Vest4

0.75

MutPred

0.78

.;Loss of solvent accessibility (P = 0.1077);.;

MVP

0.34

ClinPred

0.91

GERP RS

1.1

gMVP

0.60

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