3-149572892-C-T

Variant names:

• chr3-149572892-C-T
• rs757669865
• NM_015472.6:c.540G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_015472.6(WWTR1):​c.540G>A​(p.Arg180Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: WWTR1 NM_015472.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503
• 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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.503 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 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.540G>A	p.Arg180Arg	synonymous	Exon 3 of 7	NP_056287.1	Q9GZV5
	WWTR1	NM_001168278.3		c.540G>A	p.Arg180Arg	synonymous	Exon 4 of 8	NP_001161750.1	Q9GZV5
	WWTR1	NM_001168280.3		c.540G>A	p.Arg180Arg	synonymous	Exon 3 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.540G>A	p.Arg180Arg	synonymous	Exon 3 of 7	ENSP00000353847.3	Q9GZV5
	WWTR1	ENST00000465804.5	TSL:2	c.540G>A	p.Arg180Arg	synonymous	Exon 4 of 8	ENSP00000419465.1	Q9GZV5
	WWTR1	ENST00000467467.5	TSL:5	c.540G>A	p.Arg180Arg	synonymous	Exon 3 of 7	ENSP00000419234.1	Q9GZV5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461802 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs757669865; hg19: chr3-149290679;