Variant 6-110101911-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003931.3(WASF1):c.1199T>C(p.Val400Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

WASF1
NM_003931.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.087438434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASF1	NM_003931.3 link	c.1199T>C	p.Val400Ala	missense_variant	10/11	ENST00000392589.6	NP_003922.1	Q92558
WASF1	NM_001024934.2 link	c.1199T>C	p.Val400Ala	missense_variant	9/10		NP_001020105.1	Q92558
WASF1	NM_001024935.2 link	c.1199T>C	p.Val400Ala	missense_variant	9/10		NP_001020106.1	Q92558
WASF1	NM_001024936.2 link	c.1199T>C	p.Val400Ala	missense_variant	8/9		NP_001020107.1	Q92558

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASF1	ENST00000392589.6 link	c.1199T>C	p.Val400Ala	missense_variant	10/11	5	NM_003931.3	ENSP00000376368.1		Q92558

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

248744

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460352

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000448

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.1199T>C (p.V400A) alteration is located in exon 10 (coding exon 7) of the WASF1 gene. This alteration results from a T to C substitution at nucleotide position 1199, causing the valine (V) at amino acid position 400 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

Benign

0.081

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.052

T;T;T;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.61

.;.;.;.;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.087

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.090

N;N;N;N;N

REVEL

Benign

0.038

Sift

Benign

0.13

T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.20

MutPred

0.31

Gain of glycosylation at P399 (P = 0.0557);Gain of glycosylation at P399 (P = 0.0557);Gain of glycosylation at P399 (P = 0.0557);Gain of glycosylation at P399 (P = 0.0557);Gain of glycosylation at P399 (P = 0.0557);

MVP

0.13

MPC

0.67

ClinPred

0.18

GERP RS

4.4

Varity_R

0.041

gMVP

0.14

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

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