Variant 6-110100526-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003931.3(WASF1):c.1676A>G(p.Glu559Gly) 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WASF1
NM_003931.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

WASF1 (HGNC:12732): (WASP family member 1) The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role downstream of Rac, a Rho-family small GTPase, in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

WASF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
WASF1	NM_003931.3 linkuse as main transcript	c.1676A>G	p.Glu559Gly	missense_variant	11/11	ENST00000392589.6	NP_003922.1
WASF1	NM_001024934.2 linkuse as main transcript	c.1676A>G	p.Glu559Gly	missense_variant	10/10		NP_001020105.1
WASF1	NM_001024935.2 linkuse as main transcript	c.1676A>G	p.Glu559Gly	missense_variant	10/10		NP_001020106.1
WASF1	NM_001024936.2 linkuse as main transcript	c.1676A>G	p.Glu559Gly	missense_variant	9/9		NP_001020107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASF1	ENST00000392589.6 linkuse as main transcript	c.1676A>G	p.Glu559Gly	missense_variant	11/11	5	NM_003931.3	ENSP00000376368	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457616

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724966

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

D;D;D;D;D

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

.;.;.;.;D

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.45

T;T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.5

L;L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.50

MutPred

0.36

Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);

MVP

0.10

MPC

1.6

ClinPred

0.99

GERP RS

5.6

Varity_R

0.56

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over