Genetic Variant NM_002444.3:c.75C>T (chrX-65716880-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_002444.3(MSN):c.75C>T(p.Thr25Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,207,654 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T25T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000012 ( 0 hom. 5 hem. )

Consequence

MSN
NM_002444.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.99

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP7

Synonymous conserved (PhyloP=-1.99 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

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.75C>T	p.Thr25Thr	synonymous	Exon 2 of 13	NP_002435.1	P26038
	MSN	NM_001440778.1		c.78C>T	p.Thr26Thr	synonymous	Exon 2 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.75C>T	p.Thr25Thr	synonymous	Exon 2 of 13	ENSP00000353408.5	P26038
MSN	ENST00000943362.1		c.75C>T	p.Thr25Thr	synonymous	Exon 3 of 14	ENSP00000613421.1
MSN	ENST00000915048.1		c.75C>T	p.Thr25Thr	synonymous	Exon 2 of 13	ENSP00000585107.1

Frequencies

GnomAD3 genomes

AF:

0.0000182

AC:

AN:

109892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000332

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000218

AC:

AN:

183088

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000145

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1097762

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26388

American (AMR)

AF:

0.00

AC:

AN:

35194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30193

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54141

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40508

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

841745

Other (OTH)

AF:

0.00

AC:

AN:

46078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000182

AC:

AN:

109892

Hom.:

Cov.:

AF XY:

0.0000311

AC XY:

AN XY:

32110

show subpopulations

African (AFR)

AF:

0.0000332

AC:

AN:

30136

American (AMR)

AF:

0.00

AC:

AN:

10245

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2616

East Asian (EAS)

AF:

0.00

AC:

AN:

3521

South Asian (SAS)

AF:

0.00

AC:

AN:

2476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

52679

Other (OTH)

AF:

0.00

AC:

AN:

1473

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.36

(source)

DANN

Benign

0.65

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over