Variant 19-34490468-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080436.2(WTIP):c.760G>A(p.Asp254Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

WTIP
NM_001080436.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

Variant links:

Genes affected

WTIP (HGNC:20964): (WT1 interacting protein) Predicted to enable transcription corepressor activity. Involved in several processes, including negative regulation of hippo signaling; positive regulation of gene silencing by miRNA; and response to hypoxia. Acts upstream of or within gene silencing by miRNA. Located in P-body. [provided by Alliance of Genome Resources, Apr 2022]

WTIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01078999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WTIP	NM_001080436.2 linkuse as main transcript	c.760G>A	p.Asp254Asn	missense_variant	2/8	ENST00000590071.7	NP_001073905.1
WTIP	XM_011526452.4 linkuse as main transcript	c.760G>A	p.Asp254Asn	missense_variant	2/8		XP_011524754.1
WTIP	XM_006723014.5 linkuse as main transcript	c.760G>A	p.Asp254Asn	missense_variant	2/8		XP_006723077.1
WTIP	XM_011526453.4 linkuse as main transcript	c.37G>A	p.Asp13Asn	missense_variant	2/8		XP_011524755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WTIP	ENST00000590071.7 linkuse as main transcript	c.760G>A	p.Asp254Asn	missense_variant	2/8	1	NM_001080436.2	ENSP00000466953	P1
WTIP	ENST00000585928.1 linkuse as main transcript	c.208G>A	p.Asp70Asn	missense_variant	2/8	3		ENSP00000465683

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000140

AC:

AN:

249152

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000127

AC:

186

AN:

1461566

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000454

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000307

Hom.:

Bravo

AF:

0.000650

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000236

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.760G>A (p.D254N) alteration is located in exon 2 (coding exon 2) of the WTIP gene. This alteration results from a G to A substitution at nucleotide position 760, causing the aspartic acid (D) at amino acid position 254 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.85

M_CAP

Benign

0.079

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.74

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

Sift4G

Benign

1.0

Vest4

0.30

MVP

0.71

MPC

0.41

ClinPred

0.041

GERP RS

2.9

Varity_R

0.064

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over