7-29834729-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080529.3(WIPF3):​c.5C>T​(p.Pro2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000529 in 1,513,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

WIPF3
NM_001080529.3 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WIPF3NM_001080529.3 linkc.5C>T p.Pro2Leu missense_variant 2/9 ENST00000242140.10 NP_001073998.2 A6NGB9
WIPF3NM_001391973.1 linkc.5C>T p.Pro2Leu missense_variant 2/8 NP_001378902.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WIPF3ENST00000242140.10 linkc.5C>T p.Pro2Leu missense_variant 2/95 NM_001080529.3 ENSP00000242140.6 A6NGB9
WIPF3ENST00000409123.5 linkc.5C>T p.Pro2Leu missense_variant 2/85 ENSP00000386790.1 A0A0A0MSG0

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000367
AC:
5
AN:
1361370
Hom.:
0
Cov.:
30
AF XY:
0.00000299
AC XY:
2
AN XY:
667988
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000575
Gnomad4 SAS exome
AF:
0.0000140
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.43e-7
Gnomad4 OTH exome
AF:
0.0000177
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

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 submitterclinical testingAmbry GeneticsJan 04, 2024The c.5C>T (p.P2L) alteration is located in exon 2 (coding exon 1) of the WIPF3 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the proline (P) at amino acid position 2 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
Pathogenic
0.88
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
25
DANN
Benign
0.95
DEOGEN2
Uncertain
0.49
.;T;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.53
T;T;.
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
0.97
.;L;L
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-3.6
D;D;D
REVEL
Uncertain
0.40
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.69
MutPred
0.24
Gain of stability (P = 0.0076);Gain of stability (P = 0.0076);Gain of stability (P = 0.0076);
MVP
0.79
MPC
0.080
ClinPred
0.60
D
GERP RS
5.1
Varity_R
0.32
gMVP
0.23

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.

Other links and lift over

dbSNP: rs563114242; hg19: chr7-29874345; API