3-149657285-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015472.6(WWTR1):​c.22C>A​(p.Pro8Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

WWTR1
NM_015472.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83
Variant links:
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]
WWTR1-AS1 (HGNC:41035): (WWTR1 antisense RNA 1)

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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=0.17842004).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WWTR1NM_015472.6 linkuse as main transcriptc.22C>A p.Pro8Thr missense_variant 2/7 ENST00000360632.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WWTR1ENST00000360632.8 linkuse as main transcriptc.22C>A p.Pro8Thr missense_variant 2/71 NM_015472.6 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsMar 06, 2023The c.22C>A (p.P8T) alteration is located in exon 2 (coding exon 1) of the WWTR1 gene. This alteration results from a C to A substitution at nucleotide position 22, causing the proline (P) at amino acid position 8 to be replaced by a threonine (T). 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
0.056
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;T;T;.;.;T;.
Eigen
Benign
-0.13
Eigen_PC
Benign
0.044
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.63
.;.;T;T;T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.18
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L;L;.;.;.;.
MutationTaster
Benign
0.96
D;D;D
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;D
REVEL
Benign
0.068
Sift
Benign
0.26
T;T;T;T;T;T;.
Sift4G
Benign
0.11
T;T;T;.;.;.;.
Polyphen
0.0
B;B;B;.;.;.;.
Vest4
0.24
MutPred
0.43
Gain of phosphorylation at P8 (P = 0.0277);Gain of phosphorylation at P8 (P = 0.0277);Gain of phosphorylation at P8 (P = 0.0277);Gain of phosphorylation at P8 (P = 0.0277);Gain of phosphorylation at P8 (P = 0.0277);Gain of phosphorylation at P8 (P = 0.0277);Gain of phosphorylation at P8 (P = 0.0277);
MVP
0.13
MPC
1.1
ClinPred
0.77
D
GERP RS
3.6
Varity_R
0.17
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-149375072; API