3-149657017-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015472.6(WWTR1):​c.290G>A​(p.Gly97Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000693 in 1,442,884 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: not found (cov: 33)
Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

WWTR1
NM_015472.6 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16903025).
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WWTR1NM_015472.6 linkuse as main transcriptc.290G>A p.Gly97Asp missense_variant 2/7 ENST00000360632.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WWTR1ENST00000360632.8 linkuse as main transcriptc.290G>A p.Gly97Asp missense_variant 2/71 NM_015472.6 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000937
AC:
2
AN:
213376
Hom.:
0
AF XY:
0.00000845
AC XY:
1
AN XY:
118384
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000603
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000105
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000693
AC:
10
AN:
1442884
Hom.:
0
Cov.:
32
AF XY:
0.00000836
AC XY:
6
AN XY:
717464
show subpopulations
Gnomad4 AFR exome
AF:
0.0000902
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000542
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000189

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 29, 2022The c.290G>A (p.G97D) alteration is located in exon 2 (coding exon 1) of the WWTR1 gene. This alteration results from a G to A substitution at nucleotide position 290, causing the glycine (G) at amino acid position 97 to be replaced by an aspartic acid (D). 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
0.59
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.42
T;T;T;.;.;T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.024
FATHMM_MKL
Benign
0.36
N
LIST_S2
Uncertain
0.87
.;.;D;D;D;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.17
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L;L;L;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.4
N;N;N;N;N;N
REVEL
Benign
0.064
Sift
Benign
0.095
T;T;T;D;D;D
Sift4G
Uncertain
0.039
D;D;D;.;.;.
Polyphen
0.0090
B;B;B;.;.;.
Vest4
0.20
MVP
0.20
MPC
0.63
ClinPred
0.24
T
GERP RS
4.2
Varity_R
0.20
gMVP
0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761456916; hg19: chr3-149374804; API