Variant chr19-34494587-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080436.2(WTIP):c.1033G>A(p.Val345Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000806 in 1,613,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

WTIP
NM_001080436.2 missense, splice_region

Scores

Splicing: ADA: 0.9557

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.346182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WTIP	NM_001080436.2 linkuse as main transcript	c.1033G>A	p.Val345Ile	missense_variant, splice_region_variant	6/8	ENST00000590071.7
WTIP	XM_011526452.4 linkuse as main transcript	c.1033G>A	p.Val345Ile	missense_variant, splice_region_variant	6/8
WTIP	XM_006723014.5 linkuse as main transcript	c.1033G>A	p.Val345Ile	missense_variant, splice_region_variant	6/8
WTIP	XM_011526453.4 linkuse as main transcript	c.310G>A	p.Val104Ile	missense_variant, splice_region_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WTIP	ENST00000590071.7 linkuse as main transcript	c.1033G>A	p.Val345Ile	missense_variant, splice_region_variant	6/8	1	NM_001080436.2	P1
WTIP	ENST00000585928.1 linkuse as main transcript	c.481G>A	p.Val161Ile	missense_variant, splice_region_variant	6/8	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247824

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461060

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Mar 02, 2023

The c.1033G>A (p.V345I) alteration is located in exon 6 (coding exon 6) of the WTIP gene. This alteration results from a G to A substitution at nucleotide position 1033, causing the valine (V) at amino acid position 345 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.011

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.071

MetaRNN

Benign

0.35

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

0.30

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

Sift4G

Benign

0.11

Vest4

0.35

MVP

0.60

MPC

0.67

ClinPred

0.81

GERP RS

4.8

Varity_R

0.14

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.96

dbscSNV1_RF

Pathogenic

0.73

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