Variant 7-29884000-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.506C>T(p.Pro169Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000243 in 1,527,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

WIPF3
NM_001080529.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

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=0.218247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF3	NM_001080529.3 linkuse as main transcript	c.506C>T	p.Pro169Leu	missense_variant	5/9	ENST00000242140.10	NP_001073998.2	A6NGB9
WIPF3	NM_001391973.1 linkuse as main transcript	c.506C>T	p.Pro169Leu	missense_variant	5/8		NP_001378902.1
WIPF3	XM_017012522.2 linkuse as main transcript	c.473C>T	p.Pro158Leu	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.506C>T	p.Pro169Leu	missense_variant	5/9	5	NM_001080529.3	ENSP00000242140.6		A6NGB9
WIPF3	ENST00000409123.5 linkuse as main transcript	c.506C>T	p.Pro169Leu	missense_variant	5/8	5		ENSP00000386790.1		A0A0A0MSG0

Frequencies

GnomAD3 genomes

AF:

0.0000730

AC:

AN:

150750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000909

AC:

AN:

131960

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

71250

show subpopulations

Gnomad AFR exome

AF:

0.000322

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:

0.000189

Gnomad OTH exome

AF:

0.000260

GnomAD4 exome

AF:

0.000261

AC:

360

AN:

1377204

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

178

AN XY:

677376

show subpopulations

Gnomad4 AFR exome

AF:

0.0000961

Gnomad4 AMR exome

AF:

0.0000288

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:

0.000322

Gnomad4 OTH exome

AF:

0.000210

GnomAD4 genome

AF:

0.0000730

AC:

AN:

150750

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73522

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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:

0.000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000313

Hom.:

ExAC

AF:

0.0000628

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

Jul 31, 2024

The c.506C>T (p.P169L) 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 506, causing the proline (P) at amino acid position 169 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

0.20

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

.;D;D

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.67

T;T;.

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.5

.;M;M

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.35

MutPred

0.16

Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);

MVP

0.48

MPC

0.41

ClinPred

0.43

GERP RS

4.0

Varity_R

0.19

gMVP

0.37

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