7-29884030-C-T

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

2
17

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]

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
WIPF3NM_001080529.3 linkuse as main transcriptc.536C>T p.Pro179Leu missense_variant 5/9 ENST00000242140.10 NP_001073998.2 A6NGB9
WIPF3NM_001391973.1 linkuse as main transcriptc.536C>T p.Pro179Leu missense_variant 5/8 NP_001378902.1
WIPF3XM_017012522.2 linkuse as main transcriptc.503C>T p.Pro168Leu missense_variant 4/8 XP_016868011.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WIPF3ENST00000242140.10 linkuse as main transcriptc.536C>T p.Pro179Leu missense_variant 5/95 NM_001080529.3 ENSP00000242140.6 A6NGB9
WIPF3ENST00000409123.5 linkuse as main transcriptc.536C>T p.Pro179Leu missense_variant 5/85 ENSP00000386790.1 A0A0A0MSG0

Frequencies

GnomAD3 genomes
AF:
0.00000695
AC:
1
AN:
143824
Hom.:
0
Cov.:
22
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:
8
AN:
87414
Hom.:
0
AF XY:
0.0000440
AC XY:
2
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:
10
AN:
1292150
Hom.:
0
Cov.:
25
AF XY:
0.00000476
AC XY:
3
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:
1
AN:
143916
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
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 submitterclinical testingAmbry GeneticsJun 11, 2024The 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
T
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
N
LIST_S2
Benign
0.46
T;T;.
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.071
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;L;L
PrimateAI
Pathogenic
0.81
D
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
T
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.

Other links and lift over

dbSNP: rs1335184981; hg19: chr7-29923646; API