rs761456916

Variant names:

• chr3-149657017-C-G
• rs761456916
• NM_015472.6:c.290G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-149657017-C-G
• chr3-149657017-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015472.6(WWTR1):​c.290G>C​(p.Gly97Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G97D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WWTR1 NM_015472.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18382153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWTR1	NM_015472.6	c.290G>C	p.Gly97Ala	missense_variant	Exon 2 of 7	ENST00000360632.8	NP_056287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWTR1	ENST00000360632.8	c.290G>C	p.Gly97Ala	missense_variant	Exon 2 of 7	1	NM_015472.6	ENSP00000353847.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000849 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;T;.;.;T
Eigen	Benign	0.050
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.83	.;.;T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L;.;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N
REVEL	Benign	0.056
Sift	Benign	0.15	T;T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;.;.;.
Polyphen		0.73	P;P;P;.;.;.
Vest4		0.40
MutPred		0.17		Gain of glycosylation at S93 (P = 0.1275);Gain of glycosylation at S93 (P = 0.1275);Gain of glycosylation at S93 (P = 0.1275);Gain of glycosylation at S93 (P = 0.1275);Gain of glycosylation at S93 (P = 0.1275);Gain of glycosylation at S93 (P = 0.1275);
MVP		0.23
MPC		0.54
ClinPred		0.40	T
GERP RS		4.2
Varity_R		0.21
gMVP		0.35

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

Other links and lift over

dbSNP: rs761456916; hg19: chr3-149374804;