Variant chr7-29884030-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.536C>T(p.Pro179Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 1,436,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

WIPF3
NM_001080529.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

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=0.07137531).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF3	NM_001080529.3 linkuse as main transcript	c.536C>T	p.Pro179Leu	missense_variant	5/9	ENST00000242140.10	NP_001073998.2	A6NGB9
WIPF3	NM_001391973.1 linkuse as main transcript	c.536C>T	p.Pro179Leu	missense_variant	5/8		NP_001378902.1
WIPF3	XM_017012522.2 linkuse as main transcript	c.503C>T	p.Pro168Leu	missense_variant	4/8		XP_016868011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF3	ENST00000242140.10 linkuse as main transcript	c.536C>T	p.Pro179Leu	missense_variant	5/9	5	NM_001080529.3	ENSP00000242140.6		A6NGB9
WIPF3	ENST00000409123.5 linkuse as main transcript	c.536C>T	p.Pro179Leu	missense_variant	5/8	5		ENSP00000386790.1		A0A0A0MSG0

Frequencies

GnomAD3 genomes

AF:

0.00000695

AC:

AN:

143824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000682

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

87414

Hom.:

AF XY:

0.0000440

AC XY:

AN XY:

45406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000367

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:

0.00

Gnomad OTH exome

AF:

0.000371

GnomAD4 exome

AF:

0.00000774

AC:

AN:

1292150

Hom.:

Cov.:

AF XY:

0.00000476

AC XY:

AN XY:

630046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000310

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:

0.00

Gnomad4 OTH exome

AF:

0.0000186

GnomAD4 genome

AF:

0.00000695

AC:

AN:

143916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69962

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000681

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

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

Jun 11, 2024

The c.536C>T (p.P179L) 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 536, causing the proline (P) at amino acid position 179 to be replaced by a leucine (L). 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

0.066

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.7

DANN

Benign

0.61

DEOGEN2

Benign

0.17

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.46

T;T;.

M_CAP

Benign

0.029

MetaRNN

Benign

0.071

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.032

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.19

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.19

MutPred

0.36

Loss of glycosylation at P179 (P = 0.0011);Loss of glycosylation at P179 (P = 0.0011);Loss of glycosylation at P179 (P = 0.0011);

MVP

0.048

MPC

0.41

ClinPred

0.074

GERP RS

-0.22

Varity_R

0.056

gMVP

0.21

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