chr13-26642314-G-A

Variant names:

• chr13-26642314-G-A
• rs755864030
• NM_006646.6:c.44G>A

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.33

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]

ACMG classification

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 rank	MANE	Protein	UniProt
WASF3	NM_006646.6	c.44G>A	p.Arg15Gln	missense_variant	Exon 3 of 10	ENST00000335327.6	NP_006637.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASF3	ENST00000335327.6	c.44G>A	p.Arg15Gln	missense_variant	Exon 3 of 10	1	NM_006646.6	ENSP00000335055.5
WASF3	ENST00000361042.8	c.44G>A	p.Arg15Gln	missense_variant	Exon 3 of 10	1		ENSP00000354325.4
WASF3	ENST00000671038.1	c.44G>A	p.Arg15Gln	missense_variant	Exon 3 of 9			ENSP00000499292.1
WASF3	ENST00000496788.1	n.212G>A		non_coding_transcript_exon_variant	Exon 2 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000164 AC: 4 AN: 244074 Hom.: 0 AF XY: 0.0000227 AC XY: 3 AN XY: 132102

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: 25 AN: 1454454 Hom.: 0 Cov.: 30 AF XY: 0.0000249 AC XY: 18 AN XY: 723532

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.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.42	.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Pathogenic	0.85	D
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	D
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

Other links and lift over

dbSNP: rs755864030; hg19: chr13-27216451; COSMIC: COSV58972181; COSMIC: COSV58972181;