Genetic Variant WIPF3:p.Gly113Cys (chr7-29879122-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001080529.3(WIPF3):c.337G>T(p.Gly113Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,459,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

WIPF3
NM_001080529.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF3	NM_001080529.3 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 4 of 9	ENST00000242140.10	NP_001073998.2	A6NGB9
WIPF3	NM_001391973.1 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 4 of 8		NP_001378902.1
WIPF3	XM_017012522.2 link	c.304G>T	p.Gly102Cys	missense_variant	Exon 3 of 8		XP_016868011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF3	ENST00000242140.10 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 4 of 9	5	NM_001080529.3	ENSP00000242140.6		A6NGB9
WIPF3	ENST00000409123.5 link	c.337G>T	p.Gly113Cys	missense_variant	Exon 4 of 8	5		ENSP00000386790.1		A0A0A0MSG0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248258

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

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:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459754

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.337G>T (p.G113C) alteration is located in exon 4 (coding exon 3) of the WIPF3 gene. This alteration results from a G to T substitution at nucleotide position 337, causing the glycine (G) at amino acid position 113 to be replaced by a cysteine (C). 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

Pathogenic

0.67

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

.;D;D

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D;.

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Uncertain

0.027

MutationAssessor

Uncertain

2.5

.;M;M

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-6.8

D;D;D

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.88

MutPred

0.25

Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);

MVP

0.90

MPC

0.46

ClinPred

0.99

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.86

gMVP

0.59

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