12-3019147-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003213.4(TEAD4):āc.560T>Cā(p.Val187Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,613,904 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 (ā ).
Frequency
Genomes: š 0.000066 ( 0 hom., cov: 33)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
TEAD4
NM_003213.4 missense
NM_003213.4 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 7.14
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]
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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=0.16546422).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TEAD4 | NM_003213.4 | c.560T>C | p.Val187Ala | missense_variant | 8/13 | ENST00000359864.8 | |
TEAD4 | NM_201441.3 | c.431T>C | p.Val144Ala | missense_variant | 7/12 | ||
TEAD4 | NM_201443.3 | c.173T>C | p.Val58Ala | missense_variant | 6/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TEAD4 | ENST00000359864.8 | c.560T>C | p.Val187Ala | missense_variant | 8/13 | 1 | NM_003213.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251220Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135808
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461734Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727180
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74338
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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 | Apr 17, 2023 | The c.560T>C (p.V187A) alteration is located in exon 8 (coding exon 6) of the TEAD4 gene. This alteration results from a T to C substitution at nucleotide position 560, causing the valine (V) at amino acid position 187 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Vest4
0.52
MutPred
0.37
.;Loss of sheet (P = 0.0181);.;
MVP
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at