chr3-149656991-G-A

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

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.709
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=0.08100438).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WWTR1NM_015472.6 linkuse as main transcriptc.316C>T p.Pro106Ser missense_variant 2/7 ENST00000360632.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WWTR1ENST00000360632.8 linkuse as main transcriptc.316C>T p.Pro106Ser missense_variant 2/71 NM_015472.6 P1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152168
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000310
AC:
7
AN:
225874
Hom.:
0
AF XY:
0.0000400
AC XY:
5
AN XY:
124996
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000286
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000698
Gnomad NFE exome
AF:
0.00000983
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1447366
Hom.:
0
Cov.:
32
AF XY:
0.00000833
AC XY:
6
AN XY:
719972
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000450
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152286
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000252
AC:
3

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 GeneticsJan 29, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.41
T;T;T;.;.;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.63
.;.;T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.081
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M;M;.;.;.
MutationTaster
Benign
0.94
D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.2
N;N;N;D;D;D
REVEL
Benign
0.037
Sift
Benign
0.069
T;T;T;T;T;D
Sift4G
Uncertain
0.051
T;T;T;.;.;.
Polyphen
0.0080
B;B;B;.;.;.
Vest4
0.088
MVP
0.11
MPC
0.48
ClinPred
0.038
T
GERP RS
1.9
Varity_R
0.045
gMVP
0.34

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: rs758233563; hg19: chr3-149374778; API