13-26665127-T-C

Position:

• chr13-26665127-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000335327.6(WASF3):​c.233T>C​(p.Val78Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WASF3 ENST00000335327.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASF3	NM_006646.6	c.233T>C	p.Val78Ala	missense_variant	4/10	ENST00000335327.6	NP_006637.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASF3	ENST00000335327.6	c.233T>C	p.Val78Ala	missense_variant	4/10	1	NM_006646.6	ENSP00000335055	P3
WASF3	ENST00000361042.8	c.233T>C	p.Val78Ala	missense_variant	4/10	1		ENSP00000354325	A1
WASF3	ENST00000671038.1	c.233T>C	p.Val78Ala	missense_variant	4/9			ENSP00000499292
WASF3	ENST00000496788.1	n.401T>C		non_coding_transcript_exon_variant	3/6	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Aug 03, 2022

The c.233T>C (p.V78A) alteration is located in exon 1 (coding exon 1) of the WASF3 gene. This alteration results from a T to C substitution at nucleotide position 233, causing the valine (V) at amino acid position 78 to be replaced by an alanine (A). 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.8	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.8	D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.75	.;P
Vest4		0.65
MutPred		0.40		Gain of relative solvent accessibility (P = 0.025);Gain of relative solvent accessibility (P = 0.025);
MVP		0.14
MPC		0.82
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.45
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-27239264;