chr3-149656991-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015472.6(WWTR1):c.316C>T(p.Pro106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,599,652 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
WWTR1
NM_015472.6 missense
NM_015472.6 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 0.709
Genes affected
WWTR1 (HGNC:24042): (WW domain containing transcription regulator 1) Enables transcription coactivator activity. Involved in several processes, including hippo signaling; positive regulation of cell differentiation; and regulation of signal transduction. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.08100438).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WWTR1 | NM_015472.6 | c.316C>T | p.Pro106Ser | missense_variant | 2/7 | ENST00000360632.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WWTR1 | ENST00000360632.8 | c.316C>T | p.Pro106Ser | missense_variant | 2/7 | 1 | NM_015472.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000310 AC: 7AN: 225874Hom.: 0 AF XY: 0.0000400 AC XY: 5AN XY: 124996
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GnomAD4 exome AF: 0.0000104 AC: 15AN: 1447366Hom.: 0 Cov.: 32 AF XY: 0.00000833 AC XY: 6AN XY: 719972
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74462
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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 | Jan 29, 2024 | The c.316C>T (p.P106S) alteration is located in exon 2 (coding exon 1) of the WWTR1 gene. This alteration results from a C to T substitution at nucleotide position 316, causing the proline (P) at amino acid position 106 to be replaced by a serine (S). 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
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T;T;D
Sift4G
Uncertain
T;T;T;.;.;.
Polyphen
B;B;B;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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