NM_006646.6:c.722A>G

Variant names:

• chr13-26681059-A-G
• rs1281746592
• NM_006646.6:c.722A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006646.6(WASF3):​c.722A>G​(p.His241Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: WASF3 NM_006646.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.13
• Publications: 0 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]

LOC107984597 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.722A>G	p.His241Arg	missense	Exon 8 of 10	NP_006637.2
	WASF3	NM_001291965.1		c.713A>G	p.His238Arg	missense	Exon 8 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.722A>G	p.His241Arg	missense	Exon 8 of 10	ENSP00000335055.5	Q9UPY6-1
	WASF3	ENST00000361042.8	TSL:1	c.713A>G	p.His238Arg	missense	Exon 8 of 10	ENSP00000354325.4	Q9UPY6-2
	WASF3	ENST00000887339.1		c.755A>G	p.His252Arg	missense	Exon 9 of 11	ENSP00000557398.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.16
BayesDel_addAF	Benign	0.0078	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.15
Sift	Benign	0.37	T
Sift4G	Benign	0.31	T
Polyphen		0.90	P
Vest4		0.66
MutPred		0.13		Loss of glycosylation at T238 (P = 0.0601)
MVP		0.22
MPC		0.69
ClinPred		0.76	D
GERP RS		5.9
Varity_R		0.11
gMVP		0.32
Mutation Taster		=64/36	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: rs1281746592; hg19: chr13-27255196;