13-26681254-C-G

Position:

• chr13-26681254-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000335327.6(WASF3):​c.917C>G​(p.Pro306Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WASF3 ENST00000335327.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2721563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASF3	NM_006646.6	c.917C>G	p.Pro306Arg	missense_variant	8/10	ENST00000335327.6	NP_006637.2
LOC107984597	XR_001749798.2	n.1813G>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASF3	ENST00000335327.6	c.917C>G	p.Pro306Arg	missense_variant	8/10	1	NM_006646.6	ENSP00000335055	P3
WASF3	ENST00000361042.8	c.908C>G	p.Pro303Arg	missense_variant	8/10	1		ENSP00000354325	A1
WASF3	ENST00000671038.1	c.908C>G	p.Pro303Arg	missense_variant	8/9			ENSP00000499292

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2022

The c.917C>G (p.P306R) alteration is located in exon 1 (coding exon 1) of the WASF3 gene. This alteration results from a C to G substitution at nucleotide position 917, causing the proline (P) at amino acid position 306 to be replaced by an arginine (R). 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	Uncertain	0.47
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.1	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.25
Sift	Benign	0.092	T;T
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.99	.;D
Vest4		0.41
MutPred		0.33		.;Loss of glycosylation at P306 (P = 4e-04);
MVP		0.14
MPC		0.97
ClinPred		0.87	D
GERP RS		6.1
Varity_R		0.21
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-27255391;