Variant 7-29884126-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080529.3(WIPF3):c.632A>C(p.Asn211Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00012 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WIPF3
NM_001080529.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.956

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07976347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF3	NM_001080529.3 linkuse as main transcript	c.632A>C	p.Asn211Thr	missense_variant	5/9	ENST00000242140.10	NP_001073998.2	A6NGB9
WIPF3	NM_001391973.1 linkuse as main transcript	c.632A>C	p.Asn211Thr	missense_variant	5/8		NP_001378902.1
WIPF3	XM_017012522.2 linkuse as main transcript	c.599A>C	p.Asn200Thr	missense_variant	4/8		XP_016868011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF3	ENST00000242140.10 linkuse as main transcript	c.632A>C	p.Asn211Thr	missense_variant	5/9	5	NM_001080529.3	ENSP00000242140.6		A6NGB9
WIPF3	ENST00000409123.5 linkuse as main transcript	c.632A>C	p.Asn211Thr	missense_variant	5/8	5		ENSP00000386790.1		A0A0A0MSG0

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

116536

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000834

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000261

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000953

AC:

AN:

1364466

Hom.:

Cov.:

AF XY:

0.00000894

AC XY:

AN XY:

670944

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:

0.0000104

Gnomad4 OTH exome

AF:

0.0000356

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000120

AC:

AN:

116590

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

56906

show subpopulations

Gnomad4 AFR

AF:

0.000237

Gnomad4 AMR

AF:

0.0000833

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000261

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00132

Hom.:

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 submitter

clinical testing

Ambry Genetics

Apr 27, 2023

The c.632A>C (p.N211T) alteration is located in exon 5 (coding exon 4) of the WIPF3 gene. This alteration results from a A to C substitution at nucleotide position 632, causing the asparagine (N) at amino acid position 211 to be replaced by a threonine (T). 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

0.073

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.0

DANN

Benign

0.85

DEOGEN2

Benign

0.17

.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.34

T;T;.

M_CAP

Benign

0.039

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.41

.;N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.67

N;N;N

REVEL

Benign

0.025

Sift

Uncertain

0.013

D;D;D

Sift4G

Benign

0.46

T;T;T

Polyphen

0.043

.;B;B

Vest4

0.072

MutPred

0.21

Loss of catalytic residue at N211 (P = 0.0226);Loss of catalytic residue at N211 (P = 0.0226);Loss of catalytic residue at N211 (P = 0.0226);

MVP

0.055

MPC

0.080

ClinPred

0.037

GERP RS

-2.4

Varity_R

0.083

gMVP

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over