Variant 11-12764285-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021961.6(TEAD1):c.53G>A(p.Arg18Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 1,614,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TEAD1
NM_021961.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.11

Variant links:

Genes affected

TEAD1 (HGNC:11714): (TEA domain transcription factor 1) This gene encodes a ubiquitous transcriptional enhancer factor that is a member of the TEA/ATTS domain family. This protein directs the transactivation of a wide variety of genes and, in placental cells, also acts as a transcriptional repressor. Mutations in this gene cause Sveinsson's chorioretinal atrophy. Additional transcript variants have been described but their full-length natures have not been experimentally verified. [provided by RefSeq, May 2010]

TEAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21082082).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEAD1	NM_021961.6 linkuse as main transcript	c.53G>A	p.Arg18Lys	missense_variant	3/13	ENST00000527636.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEAD1	ENST00000527636.7 linkuse as main transcript	c.53G>A	p.Arg18Lys	missense_variant	3/13	1	NM_021961.6		P28347-1
TEAD1	ENST00000334310.10 linkuse as main transcript	c.8G>A	p.Arg3Lys	missense_variant	2/12	1		P1	P28347-2
TEAD1	ENST00000527575.6 linkuse as main transcript	c.53G>A	p.Arg18Lys	missense_variant	2/11	5
TEAD1	ENST00000527376.3 linkuse as main transcript	c.53G>A	p.Arg18Lys	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251298

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.53G>A (p.R18K) alteration is located in exon 3 (coding exon 1) of the TEAD1 gene. This alteration results from a G to A substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

T;T;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.69

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.10

N;N;N;.

REVEL

Benign

0.14

Sift

Benign

0.81

T;T;T;.

Sift4G

Benign

0.78

T;T;T;.

Polyphen

0.41

.;.;.;B

Vest4

0.56

MutPred

0.33

Gain of ubiquitination at R18 (P = 0.0018);Gain of ubiquitination at R18 (P = 0.0018);.;Gain of ubiquitination at R18 (P = 0.0018);

MVP

0.49

ClinPred

0.31

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.41

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