Genetic Variant NM_006646.6:c.752C>T (chr13-26681089-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_006646.6(WASF3):c.752C>T(p.Pro251Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000449 in 1,614,082 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 2 hom. )

Consequence

WASF3
NM_006646.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

Publications

2 publications found

Variant links:

Genes affected

WASF3 (HGNC:12734): (WASP family member 3) This gene encodes a member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that links receptor kinases and actin. Binding to actin occurs through a C-terminal verprolin homology domain in all family members. The multiprotein complex serves to tranduce signals that involve changes in cell shape, motility or function. A pseudogene of this gene have been defined on chromosome 6. Alternative splicing results in multiple transcript variants [provided by RefSeq, May 2014]

WASF3 links:

LOC107984597 (HGNC:):

LOC107984597 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3424667).

BS2

High AC in GnomAd4 at 42 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006646.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASF3	NM_006646.6	MANE Select	c.752C>T	p.Pro251Leu	missense	Exon 8 of 10	NP_006637.2
	WASF3	NM_001291965.1		c.743C>T	p.Pro248Leu	missense	Exon 8 of 10	NP_001278894.1	Q9UPY6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WASF3	ENST00000335327.6	TSL:1 MANE Select	c.752C>T	p.Pro251Leu	missense	Exon 8 of 10	ENSP00000335055.5	Q9UPY6-1
WASF3	ENST00000361042.8	TSL:1	c.743C>T	p.Pro248Leu	missense	Exon 8 of 10	ENSP00000354325.4	Q9UPY6-2
WASF3	ENST00000887339.1		c.785C>T	p.Pro262Leu	missense	Exon 9 of 11	ENSP00000557398.1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000353

AC:

AN:

249466

AF XY:

0.000482

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000447

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000467

AC:

683

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

365

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.000134

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00107

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000502

AC:

558

AN:

1111952

Other (OTH)

AF:

0.000315

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000276

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41562

American (AMR)

AF:

0.000261

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000362

Hom.:

Bravo

AF:

0.000298

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000387

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000534

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.035

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.0

PhyloP100

6.0

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.23

Sift

Benign

0.060

Sift4G

Benign

0.14

Polyphen

0.86

Vest4

0.78

MVP

0.31

MPC

0.54

ClinPred

0.11

GERP RS

5.9

Varity_R

0.076

gMVP

0.48

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over