chr3-149520981-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015472.6(WWTR1):​c.1027G>A​(p.Ala343Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,592,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

WWTR1
NM_015472.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0820
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.015779763).
BS2
High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WWTR1NM_015472.6 linkuse as main transcriptc.1027G>A p.Ala343Thr missense_variant 7/7 ENST00000360632.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WWTR1ENST00000360632.8 linkuse as main transcriptc.1027G>A p.Ala343Thr missense_variant 7/71 NM_015472.6 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152152
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000613
AC:
14
AN:
228260
Hom.:
0
AF XY:
0.0000486
AC XY:
6
AN XY:
123444
show subpopulations
Gnomad AFR exome
AF:
0.0000642
Gnomad AMR exome
AF:
0.000142
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000118
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000653
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000181
AC:
26
AN:
1440008
Hom.:
0
Cov.:
30
AF XY:
0.0000223
AC XY:
16
AN XY:
715950
show subpopulations
Gnomad4 AFR exome
AF:
0.0000627
Gnomad4 AMR exome
AF:
0.000153
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000764
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000118
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152270
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000178
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000741
AC:
9

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 GeneticsJun 17, 2024The c.1027G>A (p.A343T) alteration is located in exon 7 (coding exon 6) of the WWTR1 gene. This alteration results from a G to A substitution at nucleotide position 1027, causing the alanine (A) at amino acid position 343 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
0.063
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
15
DANN
Benign
0.76
DEOGEN2
Benign
0.21
T;T;T;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.64
.;.;T;T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.016
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.25
N;N;N;N
REVEL
Benign
0.035
Sift
Benign
0.57
T;T;T;T
Sift4G
Benign
0.64
T;T;T;T
Polyphen
0.15
B;B;B;.
Vest4
0.020
MVP
0.12
MPC
0.46
ClinPred
0.0061
T
GERP RS
1.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.017
gMVP
0.19

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

LitVar

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

Other links and lift over

dbSNP: rs188215356; hg19: chr3-149238768; COSMIC: COSV105257563; COSMIC: COSV105257563; API