rs755864030

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R15G) has been classified 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
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 25 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.44G>A	p.Arg15Gln	missense	Exon 3 of 10	NP_006637.2
	WASF3	NM_001291965.1		c.44G>A	p.Arg15Gln	missense	Exon 3 of 10	NP_001278894.1	Q9UPY6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASF3	ENST00000335327.6	TSL:1 MANE Select	c.44G>A	p.Arg15Gln	missense	Exon 3 of 10	ENSP00000335055.5	Q9UPY6-1
	WASF3	ENST00000361042.8	TSL:1	c.44G>A	p.Arg15Gln	missense	Exon 3 of 10	ENSP00000354325.4	Q9UPY6-2
	WASF3	ENST00000887339.1		c.44G>A	p.Arg15Gln	missense	Exon 3 of 11	ENSP00000557398.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 244074 AF XY: 0.0000227

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 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

African (AFR) AF: 0.0000303 AC: 1 AN: 32984

American (AMR) AF: 0.00 AC: 0 AN: 42930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25940

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39256

South Asian (SAS) AF: 0.000130 AC: 11 AN: 84748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1109452

Other (OTH) AF: 0.00 AC: 0 AN: 60074

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.34
Sift	Benign	0.040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.95	P
Vest4		0.80
MutPred		0.49		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
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

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