Variant 11-12937202-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP3_ModeratePP5

The NM_021961.6(TEAD1):c.1261T>C(p.Tyr421His) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y421N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

TEAD1
NM_021961.6 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.02

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a strand (size 7) in uniprot entity TEAD1_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_021961.6

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr11-12937202-T-A is described in Lovd as [Likely_pathogenic].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.894

PP5

Variant 11-12937202-T-C is Pathogenic according to our data. Variant chr11-12937202-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 12630.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-12937202-T-C is described in Lovd as [Pathogenic]. Variant chr11-12937202-T-C is described in Lovd as [Likely_pathogenic]. Variant chr11-12937202-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEAD1	NM_021961.6 linkuse as main transcript	c.1261T>C	p.Tyr421His	missense_variant	13/13	ENST00000527636.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEAD1	ENST00000527636.7 linkuse as main transcript	c.1261T>C	p.Tyr421His	missense_variant	13/13	1	NM_021961.6		P28347-1
TEAD1	ENST00000334310.10 linkuse as main transcript	c.1054T>C	p.Tyr352His	missense_variant	12/12	1		P1	P28347-2
TEAD1	ENST00000526600.1 linkuse as main transcript	c.973T>C	p.Tyr325His	missense_variant	8/8	1
TEAD1	ENST00000527575.6 linkuse as main transcript	c.1087T>C	p.Tyr363His	missense_variant	11/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000118

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Helicoid peripapillary chorioretinal degeneration

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 05, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;D;.;D;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D;D;D;D

M_CAP

Pathogenic

0.44

MetaRNN

Pathogenic

0.89

D;D;D;D;D

MetaSVM

Uncertain

0.54

MutationAssessor

Uncertain

2.9

.;.;.;M;.

MutationTaster

Benign

1.0

A;A;A

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-4.5

D;D;D;.;D

REVEL

Pathogenic

0.89

Sift

Pathogenic

0.0

D;D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;.;D

Polyphen

1.0

.;.;.;D;D

Vest4

0.85, 0.91

MutPred

0.65

Gain of disorder (P = 0.0121);.;.;Gain of disorder (P = 0.0121);.;

MVP

0.86

ClinPred

0.99

GERP RS

5.7

Varity_R

0.81

gMVP

0.78

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