Variant 13-26665018-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000335327.6(WASF3):c.134-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,613,970 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 38 hom. )

Consequence

WASF3
ENST00000335327.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0006156

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.85

Variant links:

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]

WASF3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 13-26665018-T-C is Benign according to our data. Variant chr13-26665018-T-C is described in ClinVar as [Benign]. Clinvar id is 715586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 358 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASF3	NM_006646.6 linkuse as main transcript	c.134-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000335327.6	NP_006637.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
WASF3	ENST00000335327.6 linkuse as main transcript	c.134-10T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_006646.6	ENSP00000335055	P3	Q9UPY6-1
WASF3	ENST00000361042.8 linkuse as main transcript	c.134-10T>C	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000354325	A1	Q9UPY6-2
WASF3	ENST00000671038.1 linkuse as main transcript	c.134-10T>C	splice_polypyrimidine_tract_variant, intron_variant			ENSP00000499292
WASF3	ENST00000496788.1 linkuse as main transcript	n.302-10T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00304

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00346

AC:

870

AN:

251304

Hom.:

AF XY:

0.00421

AC XY:

572

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00316

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00292

AC:

4265

AN:

1461600

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

2438

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0136

Gnomad4 FIN exome

AF:

0.000394

Gnomad4 NFE exome

AF:

0.00243

Gnomad4 OTH exome

AF:

0.00303

GnomAD4 genome

AF:

0.00235

AC:

358

AN:

152370

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0126

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00304

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00300

Hom.:

Bravo

AF:

0.00201

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00062

dbscSNV1_RF

Benign

0.014

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over