Genetic Variant WWTR1:p.Gly97Asp (chr3-149657017-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Publications

0 publications found

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 links:

WWTR1-AS1 (HGNC:41035): (WWTR1 antisense RNA 1)

WWTR1-AS1 links:

ENSG00000301802 (HGNC:):

ENSG00000301802 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16903025).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015472.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WWTR1	NM_015472.6	MANE Select	c.290G>A	p.Gly97Asp	missense	Exon 2 of 7	NP_056287.1	Q9GZV5
WWTR1	NM_001168278.3		c.290G>A	p.Gly97Asp	missense	Exon 3 of 8	NP_001161750.1	Q9GZV5
WWTR1	NM_001168280.3		c.290G>A	p.Gly97Asp	missense	Exon 2 of 7	NP_001161752.1	Q9GZV5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WWTR1	ENST00000360632.8	TSL:1 MANE Select	c.290G>A	p.Gly97Asp	missense	Exon 2 of 7	ENSP00000353847.3	Q9GZV5
WWTR1	ENST00000465804.5	TSL:2	c.290G>A	p.Gly97Asp	missense	Exon 3 of 8	ENSP00000419465.1	Q9GZV5
WWTR1	ENST00000467467.5	TSL:5	c.290G>A	p.Gly97Asp	missense	Exon 2 of 7	ENSP00000419234.1	Q9GZV5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000937

AC:

AN:

213376

AF XY:

0.00000845

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000693

AC:

AN:

1442884

Hom.:

Cov.:

AF XY:

0.00000836

AC XY:

AN XY:

717464

show subpopulations

African (AFR)

AF:

0.0000902

AC:

AN:

33258

American (AMR)

AF:

0.00

AC:

AN:

43364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25748

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39406

South Asian (SAS)

AF:

0.00

AC:

AN:

85324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42808

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.00000542

AC:

AN:

1107540

Other (OTH)

AF:

0.00

AC:

AN:

59804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.024

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.019

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

3.7

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.4

REVEL

Benign

0.064

Sift

Benign

0.095

Sift4G

Uncertain

0.039

Polyphen

0.0090

Vest4

0.20

MVP

0.20

MPC

0.63

ClinPred

0.24

GERP RS

4.2

PromoterAI

0.0018

Neutral

(source)

Varity_R

0.20

gMVP

0.41

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over