3-149657111-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015472.6(WWTR1):ā€‹c.196A>Gā€‹(p.Ser66Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

WWTR1
NM_015472.6 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.01
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WWTR1NM_015472.6 linkuse as main transcriptc.196A>G p.Ser66Gly missense_variant 2/7 ENST00000360632.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WWTR1ENST00000360632.8 linkuse as main transcriptc.196A>G p.Ser66Gly missense_variant 2/71 NM_015472.6 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1431632
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
710014
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 GeneticsApr 26, 2023The c.196A>G (p.S66G) alteration is located in exon 2 (coding exon 1) of the WWTR1 gene. This alteration results from a A to G substitution at nucleotide position 196, causing the serine (S) at amino acid position 66 to be replaced by a glycine (G). 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
Pathogenic
0.91
BayesDel_addAF
Uncertain
0.042
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.78
D;D;D;.;.;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
.;.;D;D;D;D
M_CAP
Uncertain
0.26
D
MetaRNN
Uncertain
0.47
T;T;T;T;T;T
MetaSVM
Benign
-0.43
T
MutationAssessor
Uncertain
2.7
M;M;M;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.0
D;D;D;D;D;D
REVEL
Benign
0.24
Sift
Benign
0.039
D;D;D;D;T;D
Sift4G
Benign
0.086
T;T;T;.;.;.
Polyphen
0.96
P;P;P;.;.;.
Vest4
0.51
MutPred
0.19
Loss of phosphorylation at S66 (P = 0.0035);Loss of phosphorylation at S66 (P = 0.0035);Loss of phosphorylation at S66 (P = 0.0035);Loss of phosphorylation at S66 (P = 0.0035);Loss of phosphorylation at S66 (P = 0.0035);Loss of phosphorylation at S66 (P = 0.0035);
MVP
0.34
MPC
1.3
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.41
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-149374898; API