Genetic Variant NM_002444.3:c.511C>T (chrX-65731150-C-T) – ACMG Classification: Pathogenic (14 pts)

Variant summary

Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong

The NM_002444.3(MSN):c.511C>T(p.Arg171Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MSN
NM_002444.3 missense

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 2.50

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

combined immunodeficiency due to moesin deficiency
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

MSN links:

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.945

PP5

Variant X-65731150-C-T is Pathogenic according to our data. Variant chrX-65731150-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 372154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002444.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSN	NM_002444.3	MANE Select	c.511C>T	p.Arg171Trp	missense	Exon 5 of 13	NP_002435.1	P26038
	MSN	NM_001440778.1		c.514C>T	p.Arg172Trp	missense	Exon 5 of 13	NP_001427707.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSN	ENST00000360270.7	TSL:1 MANE Select	c.511C>T	p.Arg171Trp	missense	Exon 5 of 13	ENSP00000353408.5	P26038
MSN	ENST00000943362.1		c.511C>T	p.Arg171Trp	missense	Exon 6 of 14	ENSP00000613421.1
MSN	ENST00000915048.1		c.511C>T	p.Arg171Trp	missense	Exon 5 of 13	ENSP00000585107.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1094224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

360044

African (AFR)

AF:

0.00

AC:

AN:

26357

American (AMR)

AF:

0.00

AC:

AN:

34868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19291

East Asian (EAS)

AF:

0.00

AC:

AN:

30112

South Asian (SAS)

AF:

0.00

AC:

AN:

53069

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40277

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840158

Other (OTH)

AF:

0.00

AC:

AN:

45976

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined immunodeficiency due to moesin deficiency (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.94

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.88

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.66

MutationAssessor

Pathogenic

4.2

PhyloP100

2.5

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.9

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.93

MutPred

0.63

Loss of disorder (P = 0.0457)

MVP

0.97

MPC

2.0

ClinPred

1.0

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.92

gMVP

0.86

Mutation Taster

=12/88

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over