chr7-29884000-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.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

1
9
9

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]

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
WIPF3NM_001080529.3 linkuse as main transcriptc.506C>T p.Pro169Leu missense_variant 5/9 ENST00000242140.10 NP_001073998.2 A6NGB9
WIPF3NM_001391973.1 linkuse as main transcriptc.506C>T p.Pro169Leu missense_variant 5/8 NP_001378902.1
WIPF3XM_017012522.2 linkuse as main transcriptc.473C>T p.Pro158Leu 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.506C>T p.Pro169Leu missense_variant 5/95 NM_001080529.3 ENSP00000242140.6 A6NGB9
WIPF3ENST00000409123.5 linkuse as main transcriptc.506C>T p.Pro169Leu missense_variant 5/85 ENSP00000386790.1 A0A0A0MSG0

Frequencies

GnomAD3 genomes
AF:
0.0000730
AC:
11
AN:
150750
Hom.:
0
Cov.:
30
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:
12
AN:
131960
Hom.:
0
AF XY:
0.000126
AC XY:
9
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.:
0
Cov.:
34
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:
11
AN:
150750
Hom.:
0
Cov.:
30
AF XY:
0.0000136
AC XY:
1
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.:
0
ExAC
AF:
0.0000628
AC:
4

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 GeneticsJul 31, 2024The 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
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.66
.;D;D
Eigen
Uncertain
0.30
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.67
T;T;.
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.5
.;M;M
PrimateAI
Pathogenic
0.87
D
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
T
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.

Other links and lift over

dbSNP: rs781472174; hg19: chr7-29923616; API