Variant 13-26642314-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006646.6(WASF3):c.44G>A(p.Arg15Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000172 in 1,454,454 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

WASF3
NM_006646.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASF3	NM_006646.6 link	c.44G>A	p.Arg15Gln	missense_variant	3/10	ENST00000335327.6	NP_006637.2	Q9UPY6-1Q5T8P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WASF3	ENST00000335327.6 link	c.44G>A	p.Arg15Gln	missense_variant	3/10	1	NM_006646.6	ENSP00000335055.5	Q9UPY6-1
WASF3	ENST00000361042.8 link	c.44G>A	p.Arg15Gln	missense_variant	3/10	1		ENSP00000354325.4	Q9UPY6-2
WASF3	ENST00000671038.1 link	c.44G>A	p.Arg15Gln	missense_variant	3/9			ENSP00000499292.1	A0A590UJ74
WASF3	ENST00000496788.1 link	n.212G>A		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

244074

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1454454

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

723532

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000811

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 12, 2024

The c.44G>A (p.R15Q) alteration is located in exon 1 (coding exon 1) of the WASF3 gene. This alteration results from a G to A substitution at nucleotide position 44, causing the arginine (R) at amino acid position 15 to be replaced by a glutamine (Q). 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

0.19

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.4

L;L

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.0

D;D

REVEL

Uncertain

0.34

Sift

Benign

0.040

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.95

.;P

Vest4

0.80

MutPred

0.49

Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);

MVP

0.32

MPC

0.92

ClinPred

0.70

GERP RS

4.6

Varity_R

0.41

gMVP

0.83

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