13-26681265-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006646.6(WASF3):ā€‹c.928C>Gā€‹(p.Pro310Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00551 in 1,613,400 control chromosomes in the GnomAD database, including 40 homozygotes. 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 Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0034 ( 0 hom., cov: 32)
Exomes š‘“: 0.0057 ( 40 hom. )

Consequence

WASF3
NM_006646.6 missense

Scores

1
1
17

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.54
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.007344365).
BP6
Variant 13-26681265-C-G is Benign according to our data. Variant chr13-26681265-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 776903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 515 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WASF3NM_006646.6 linkuse as main transcriptc.928C>G p.Pro310Ala missense_variant 8/10 ENST00000335327.6 NP_006637.2
LOC107984597XR_001749798.2 linkuse as main transcriptn.1802G>C non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WASF3ENST00000335327.6 linkuse as main transcriptc.928C>G p.Pro310Ala missense_variant 8/101 NM_006646.6 ENSP00000335055 P3Q9UPY6-1
WASF3ENST00000361042.8 linkuse as main transcriptc.919C>G p.Pro307Ala missense_variant 8/101 ENSP00000354325 A1Q9UPY6-2
WASF3ENST00000671038.1 linkuse as main transcriptc.919C>G p.Pro307Ala missense_variant 8/9 ENSP00000499292

Frequencies

GnomAD3 genomes
AF:
0.00338
AC:
515
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00150
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00614
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00363
AC:
888
AN:
244360
Hom.:
6
AF XY:
0.00361
AC XY:
481
AN XY:
133350
show subpopulations
Gnomad AFR exome
AF:
0.000950
Gnomad AMR exome
AF:
0.00323
Gnomad ASJ exome
AF:
0.00222
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00109
Gnomad FIN exome
AF:
0.00168
Gnomad NFE exome
AF:
0.00576
Gnomad OTH exome
AF:
0.00716
GnomAD4 exome
AF:
0.00573
AC:
8369
AN:
1461074
Hom.:
40
Cov.:
34
AF XY:
0.00566
AC XY:
4114
AN XY:
726808
show subpopulations
Gnomad4 AFR exome
AF:
0.00105
Gnomad4 AMR exome
AF:
0.00293
Gnomad4 ASJ exome
AF:
0.00226
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00132
Gnomad4 FIN exome
AF:
0.00200
Gnomad4 NFE exome
AF:
0.00686
Gnomad4 OTH exome
AF:
0.00477
GnomAD4 genome
AF:
0.00338
AC:
515
AN:
152326
Hom.:
0
Cov.:
32
AF XY:
0.00317
AC XY:
236
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.00614
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00514
Hom.:
2
Bravo
AF:
0.00337
TwinsUK
AF:
0.00485
AC:
18
ALSPAC
AF:
0.00441
AC:
17
ESP6500AA
AF:
0.000685
AC:
3
ESP6500EA
AF:
0.00609
AC:
52
ExAC
AF:
0.00381
AC:
461
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00518
EpiControl
AF:
0.00439

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023WASF3: BS2 -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
14
DANN
Benign
0.90
DEOGEN2
Benign
0.072
.;T
Eigen
Benign
-0.11
Eigen_PC
Benign
0.0049
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.0073
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.94
.;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.13
Sift
Benign
0.14
T;T
Sift4G
Benign
0.28
T;T
Polyphen
0.16
.;B
Vest4
0.54
MVP
0.14
MPC
0.84
ClinPred
0.026
T
GERP RS
6.1
Varity_R
0.042
gMVP
0.18

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: rs151322145; hg19: chr13-27255402; COSMIC: COSV105243758; COSMIC: COSV105243758; API