chr3-149656960-T-C

Variant names:

• chr3-149656960-T-C
• rs763707772
• NM_015472.6:c.347A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015472.6(WWTR1):​c.347A>G​(p.Gln116Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000526 in 1,596,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: WWTR1 NM_015472.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

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)

ENSG00000301802 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011953324).
• BS2: High AC in GnomAd4 at 11 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWTR1	NM_015472.6	MANE Select	c.347A>G	p.Gln116Arg	missense	Exon 2 of 7	NP_056287.1	Q9GZV5
	WWTR1	NM_001168278.3		c.347A>G	p.Gln116Arg	missense	Exon 3 of 8	NP_001161750.1	Q9GZV5
	WWTR1	NM_001168280.3		c.347A>G	p.Gln116Arg	missense	Exon 2 of 7	NP_001161752.1	Q9GZV5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWTR1	ENST00000360632.8	TSL:1 MANE Select	c.347A>G	p.Gln116Arg	missense	Exon 2 of 7	ENSP00000353847.3	Q9GZV5
	WWTR1	ENST00000465804.5	TSL:2	c.347A>G	p.Gln116Arg	missense	Exon 3 of 8	ENSP00000419465.1	Q9GZV5
	WWTR1	ENST00000467467.5	TSL:5	c.347A>G	p.Gln116Arg	missense	Exon 2 of 7	ENSP00000419234.1	Q9GZV5

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00260

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

GnomAD2 exomes AF: 0.000109 AC: 25 AN: 229178 AF XY: 0.000119

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00239

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000192

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000505 AC: 73 AN: 1444150 Hom.: 0 Cov.: 32 AF XY: 0.0000585 AC XY: 42 AN XY: 718080

African (AFR) AF: 0.00 AC: 0 AN: 32678

American (AMR) AF: 0.00 AC: 0 AN: 42876

Ashkenazi Jewish (ASJ) AF: 0.00220 AC: 56 AN: 25430

East Asian (EAS) AF: 0.00 AC: 0 AN: 39280

South Asian (SAS) AF: 0.00 AC: 0 AN: 84456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 0.00000542 AC: 6 AN: 1107088

Other (OTH) AF: 0.000184 AC: 11 AN: 59758

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000565 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000662 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Benign	0.76
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.35	N
PhyloP100		1.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.25		Gain of solvent accessibility (P = 0.0086)
MVP		0.12
MPC		0.52
ClinPred		0.014	T
GERP RS		3.9
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.42
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs763707772; hg19: chr3-149374747;