Variant X-65716828-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS2

The NM_002444.3(MSN):c.23G>A(p.Arg8His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,206,923 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000021 ( 0 hom. 7 hem. )

Consequence

MSN
NM_002444.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.65

Variant links:

Genes affected

MSN (HGNC:7373): (moesin) Moesin (for membrane-organizing extension spike protein) is a member of the ERM family which includes ezrin and radixin. ERM proteins appear to function as cross-linkers between plasma membranes and actin-based cytoskeletons. Moesin is localized to filopodia and other membranous protrusions that are important for cell-cell recognition and signaling and for cell movement. [provided by RefSeq, Jul 2008]

MSN links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.828

BP6

Variant X-65716828-G-A is Benign according to our data. Variant chrX-65716828-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1673843.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSN	NM_002444.3 linkuse as main transcript	c.23G>A	p.Arg8His	missense_variant	2/13	ENST00000360270.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSN	ENST00000360270.7 linkuse as main transcript	c.23G>A	p.Arg8His	missense_variant	2/13	1	NM_002444.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000274

AC:

AN:

109469

Hom.:

Cov.:

AF XY:

0.0000315

AC XY:

AN XY:

31757

show subpopulations

Gnomad AFR

AF:

0.0000333

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:

0.0000380

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000328

AC:

AN:

182896

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

67478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

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:

0.0000613

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1097454

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

362864

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000226

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000274

AC:

AN:

109469

Hom.:

Cov.:

AF XY:

0.0000315

AC XY:

AN XY:

31757

show subpopulations

Gnomad4 AFR

AF:

0.0000333

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:

0.0000380

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Uncertain

0.070

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.81

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.53

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.030

Polyphen

0.069

Vest4

0.78

MutPred

0.54

Gain of ubiquitination at K3 (P = 0.0417);

MVP

0.96

MPC

1.1

ClinPred

0.45

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

gMVP

0.58

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

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