7-29883967-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080529.3(WIPF3):​c.473C>A​(p.Ala158Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,522 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: not found (cov: 30)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

WIPF3
NM_001080529.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.204
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056577265).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WIPF3NM_001080529.3 linkc.473C>A p.Ala158Glu missense_variant Exon 5 of 9 ENST00000242140.10 NP_001073998.2 A6NGB9
WIPF3NM_001391973.1 linkc.473C>A p.Ala158Glu missense_variant Exon 5 of 8 NP_001378902.1
WIPF3XM_017012522.2 linkc.440C>A p.Ala147Glu missense_variant Exon 4 of 8 XP_016868011.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WIPF3ENST00000242140.10 linkc.473C>A p.Ala158Glu missense_variant Exon 5 of 9 5 NM_001080529.3 ENSP00000242140.6 A6NGB9
WIPF3ENST00000409123.5 linkc.473C>A p.Ala158Glu missense_variant Exon 5 of 8 5 ENSP00000386790.1 A0A0A0MSG0

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
7.17e-7
AC:
1
AN:
1395522
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
688478
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:
9.28e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.473C>A (p.A158E) alteration is located in exon 5 (coding exon 4) of the WIPF3 gene. This alteration results from a C to A substitution at nucleotide position 473, causing the alanine (A) at amino acid position 158 to be replaced by a glutamic acid (E). 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
0.16
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
16
DANN
Benign
0.83
DEOGEN2
Benign
0.19
.;T;T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.065
N
LIST_S2
Benign
0.50
T;T;.
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.057
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.26
.;N;N
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Benign
0.0080
Sift
Uncertain
0.0080
D;D;D
Sift4G
Benign
0.69
T;T;T
Polyphen
0.36
.;B;B
Vest4
0.16
MutPred
0.22
Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MVP
0.099
MPC
0.24
ClinPred
0.13
T
GERP RS
0.30
Varity_R
0.16
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs943086410; hg19: chr7-29923583; API