dbSNP rs781209832: WIPF3:p.Pro111Gln (chr7-29879117-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001080529.3(WIPF3):c.332C>A(p.Pro111Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,460,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P111R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

WIPF3
NM_001080529.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.59

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF3	NM_001080529.3 link	c.332C>A	p.Pro111Gln	missense_variant	Exon 4 of 9	ENST00000242140.10	NP_001073998.2	A6NGB9
WIPF3	NM_001391973.1 link	c.332C>A	p.Pro111Gln	missense_variant	Exon 4 of 8		NP_001378902.1
WIPF3	XM_017012522.2 link	c.299C>A	p.Pro100Gln	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.332C>A	p.Pro111Gln	missense_variant	Exon 4 of 9	5	NM_001080529.3	ENSP00000242140.6		A6NGB9
WIPF3	ENST00000409123.5 link	c.332C>A	p.Pro111Gln	missense_variant	Exon 4 of 8	5		ENSP00000386790.1		A0A0A0MSG0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

248142

Hom.:

AF XY:

0.0000520

AC XY:

AN XY:

134554

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000320

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:

0.00000890

AC:

AN:

1460010

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000269

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.77

.;D;D

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D;.

M_CAP

Benign

0.058

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

-0.088

MutationAssessor

Uncertain

2.5

.;M;M

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.81

MutPred

0.27

Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);

MVP

0.85

MPC

0.43

ClinPred

0.85

GERP RS

5.4

Varity_R

0.67

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over