13-26665033-C-T

Position:

• chr13-26665033-C-T

Variant summary

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

The ENST00000335327.6(WASF3):​c.139C>T​(p.His47Tyr) 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: 7.40

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.139C>T	p.His47Tyr	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.139C>T	p.His47Tyr	missense_variant	4/10	1	NM_006646.6	ENSP00000335055	P3
WASF3	ENST00000361042.8	c.139C>T	p.His47Tyr	missense_variant	4/10	1		ENSP00000354325	A1
WASF3	ENST00000671038.1	c.139C>T	p.His47Tyr	missense_variant	4/9			ENSP00000499292
WASF3	ENST00000496788.1	n.307C>T		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

Oct 29, 2021

The c.139C>T (p.H47Y) alteration is located in exon 1 (coding exon 1) of the WASF3 gene. This alteration results from a C to T substitution at nucleotide position 139, causing the histidine (H) at amino acid position 47 to be replaced by a tyrosine (Y). 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	0.56
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.14	T;T
Sift4G	Benign	0.41	T;T
Polyphen		1.0	.;D
Vest4		0.81
MutPred		0.38		Loss of disorder (P = 0.0559);Loss of disorder (P = 0.0559);
MVP		0.32
MPC		1.1
ClinPred		0.87	D
GERP RS		5.6
Varity_R		0.32
gMVP		0.86

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: chr13-27239170;