rs758928652

Variant names:

• chr13-26642376-G-A
• rs758928652
• NM_006646.6:c.106G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-26642376-G-A
• chr13-26642376-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006646.6(WASF3):​c.106G>A​(p.Ala36Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000623 in 1,606,372 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: WASF3 NM_006646.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51
• 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 9 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.106G>A	p.Ala36Thr	missense	Exon 3 of 10	NP_006637.2
	WASF3	NM_001291965.1		c.106G>A	p.Ala36Thr	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.106G>A	p.Ala36Thr	missense	Exon 3 of 10	ENSP00000335055.5	Q9UPY6-1
	WASF3	ENST00000361042.8	TSL:1	c.106G>A	p.Ala36Thr	missense	Exon 3 of 10	ENSP00000354325.4	Q9UPY6-2
	WASF3	ENST00000887339.1		c.106G>A	p.Ala36Thr	missense	Exon 3 of 11	ENSP00000557398.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1454178 Hom.: 0 Cov.: 30 AF XY: 0.00000415 AC XY: 3 AN XY: 723396

African (AFR) AF: 0.00 AC: 0 AN: 33014

American (AMR) AF: 0.00 AC: 0 AN: 43084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39152

South Asian (SAS) AF: 0.00 AC: 0 AN: 84722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1109076

Other (OTH) AF: 0.00 AC: 0 AN: 60080

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.28
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Benign	0.12	T
Sift4G	Uncertain	0.042	D
Polyphen		0.98	D
Vest4		0.78
MutPred		0.37		Gain of disorder (P = 0.2574)
MVP		0.14
MPC		0.94
ClinPred		0.95	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.77
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs758928652; hg19: chr13-27216513; COSMIC: COSV58965086; COSMIC: COSV58965086;