Variant 7-29884143-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080529.3(WIPF3):c.649C>T(p.Pro217Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,524,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P217H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

WIPF3
NM_001080529.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.566

Variant links:

Genes affected

WIPF3 (HGNC:22004): (WAS/WASL interacting protein family member 3) Predicted to enable SH3 domain binding activity and actin binding activity. Predicted to be involved in actin filament-based movement. Predicted to be located in cytosol. Predicted to be active in actin filament. [provided by Alliance of Genome Resources, Apr 2022]

WIPF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15300688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WIPF3	NM_001080529.3 linkuse as main transcript	c.649C>T	p.Pro217Ser	missense_variant	5/9	ENST00000242140.10
WIPF3	NM_001391973.1 linkuse as main transcript	c.649C>T	p.Pro217Ser	missense_variant	5/8
WIPF3	XM_017012522.2 linkuse as main transcript	c.616C>T	p.Pro206Ser	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIPF3	ENST00000242140.10 linkuse as main transcript	c.649C>T	p.Pro217Ser	missense_variant	5/9	5	NM_001080529.3	P5
WIPF3	ENST00000409123.5 linkuse as main transcript	c.649C>T	p.Pro217Ser	missense_variant	5/8	5		A2

Frequencies

GnomAD3 genomes

AF:

0.0000534

AC:

AN:

149824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000958

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000891

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000645

AC:

AN:

124068

Hom.:

AF XY:

0.0000753

AC XY:

AN XY:

66364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000910

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000700

Gnomad NFE exome

AF:

0.000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000204

AC:

281

AN:

1374404

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

119

AN XY:

676152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000919

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000249

Gnomad4 OTH exome

AF:

0.0000704

GnomAD4 genome

AF:

0.0000534

AC:

AN:

149912

Hom.:

Cov.:

AF XY:

0.0000821

AC XY:

AN XY:

73096

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000663

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000958

Gnomad4 NFE

AF:

0.0000892

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000579

AC:

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

Jun 12, 2023

The c.649C>T (p.P217S) alteration is located in exon 5 (coding exon 4) of the WIPF3 gene. This alteration results from a C to T substitution at nucleotide position 649, causing the proline (P) at amino acid position 217 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.50

T;T;.

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.041

Sift

Uncertain

0.012

D;D;D

Sift4G

Benign

0.070

T;T;T

Polyphen

0.057

.;B;B

Vest4

0.088

MutPred

0.22

Gain of glycosylation at P217 (P = 0.0122);Gain of glycosylation at P217 (P = 0.0122);Gain of glycosylation at P217 (P = 0.0122);

MVP

0.33

MPC

0.38

ClinPred

0.096

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.30

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