NM_015472.6:c.1074T>C

Variant names:

• chr3-149520934-A-G
• rs1294542058
• NM_015472.6:c.1074T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015472.6(WWTR1):​c.1074T>C​(p.Pro358Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,304 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: WWTR1 NM_015472.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-149520934-A-G is Benign according to our data. Variant chr3-149520934-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2578952.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BS2: High AC in GnomAd4 at 5 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.1074T>C	p.Pro358Pro	synonymous	Exon 7 of 7	NP_056287.1	Q9GZV5
	WWTR1	NM_001168278.3		c.1074T>C	p.Pro358Pro	synonymous	Exon 8 of 8	NP_001161750.1	Q9GZV5
	WWTR1	NM_001168280.3		c.1074T>C	p.Pro358Pro	synonymous	Exon 7 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.1074T>C	p.Pro358Pro	synonymous	Exon 7 of 7	ENSP00000353847.3	Q9GZV5
	WWTR1	ENST00000465804.5	TSL:2	c.1074T>C	p.Pro358Pro	synonymous	Exon 8 of 8	ENSP00000419465.1	Q9GZV5
	WWTR1	ENST00000467467.5	TSL:5	c.1074T>C	p.Pro358Pro	synonymous	Exon 7 of 7	ENSP00000419234.1	Q9GZV5

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461068 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 726768

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85988

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111674

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74388

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

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		-1.2

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: rs1294542058; hg19: chr3-149238721;