13-26665074-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000335327.6(WASF3):​c.180C>A​(p.Asn60Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

WASF3
ENST00000335327.6 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WASF3NM_006646.6 linkuse as main transcriptc.180C>A p.Asn60Lys missense_variant 4/10 ENST00000335327.6 NP_006637.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WASF3ENST00000335327.6 linkuse as main transcriptc.180C>A p.Asn60Lys missense_variant 4/101 NM_006646.6 ENSP00000335055 P3Q9UPY6-1
WASF3ENST00000361042.8 linkuse as main transcriptc.180C>A p.Asn60Lys missense_variant 4/101 ENSP00000354325 A1Q9UPY6-2
WASF3ENST00000671038.1 linkuse as main transcriptc.180C>A p.Asn60Lys missense_variant 4/9 ENSP00000499292
WASF3ENST00000496788.1 linkuse as main transcriptn.348C>A non_coding_transcript_exon_variant 3/63

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000597
AC:
15
AN:
251420
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000405
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461828
Hom.:
0
Cov.:
32
AF XY:
0.0000193
AC XY:
14
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000313
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000151
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsSep 16, 2021The c.180C>A (p.N60K) alteration is located in exon 1 (coding exon 1) of the WASF3 gene. This alteration results from a C to A substitution at nucleotide position 180, causing the asparagine (N) at amino acid position 60 to be replaced by a lysine (K). 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
Pathogenic
0.86
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
.;T
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.1
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-4.4
D;D
REVEL
Benign
0.25
Sift
Benign
0.063
T;T
Sift4G
Benign
0.071
T;T
Polyphen
0.58
.;P
Vest4
0.90
MutPred
0.37
Gain of ubiquitination at N60 (P = 0.0211);Gain of ubiquitination at N60 (P = 0.0211);
MVP
0.12
MPC
1.1
ClinPred
0.54
D
GERP RS
4.8
Varity_R
0.61
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs762542009; hg19: chr13-27239211; API