11-12764309-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_021961.6(TEAD1):c.77C>A(p.Pro26Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,614,032 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P26S) has been classified as Uncertain significance.
Frequency
Consequence
NM_021961.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TEAD1 | NM_021961.6 | c.77C>A | p.Pro26Gln | missense_variant | 3/13 | ENST00000527636.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TEAD1 | ENST00000527636.7 | c.77C>A | p.Pro26Gln | missense_variant | 3/13 | 1 | NM_021961.6 | ||
TEAD1 | ENST00000334310.10 | c.32C>A | p.Pro11Gln | missense_variant | 2/12 | 1 | P1 | ||
TEAD1 | ENST00000527575.6 | c.77C>A | p.Pro26Gln | missense_variant | 2/11 | 5 | |||
TEAD1 | ENST00000527376.3 | c.77C>A | p.Pro26Gln | missense_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251284Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135806
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727234
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74342
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.77C>A (p.P26Q) alteration is located in exon 3 (coding exon 1) of the TEAD1 gene. This alteration results from a C to A substitution at nucleotide position 77, causing the proline (P) at amino acid position 26 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 26 of the TEAD1 protein (p.Pro26Gln). This variant is present in population databases (rs756716749, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with TEAD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1036850). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at