chrX-65716908-C-T

Variant names:

• chrX-65716908-C-T
• rs372696816
• NM_002444.3:c.96+7C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002444.3(MSN):​c.96+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000537 in 1,201,022 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 189 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., 12 hem., cov: 22)
  • Exomes 𝑓: 0.00055 (0 hom. 177 hem.)
• Consequence: MSN NM_002444.3 splice_region, intron
• Scores: Splicing: ADA: 0.00005737
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0500
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-65716908-C-T is Benign according to our data. Variant chrX-65716908-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 738604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 12 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.96+7C>T		splice_region intron	N/A	NP_002435.1	P26038
	MSN	NM_001440778.1		c.99+7C>T		splice_region intron	N/A	NP_001427707.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSN	ENST00000360270.7	TSL:1 MANE Select	c.96+7C>T		splice_region intron	N/A	ENSP00000353408.5	P26038
	MSN	ENST00000943362.1		c.96+7C>T		splice_region intron	N/A	ENSP00000613421.1
	MSN	ENST00000915048.1		c.96+7C>T		splice_region intron	N/A	ENSP00000585107.1

Frequencies

GnomAD3 genomes AF: 0.000400 AC: 44 AN: 109920 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000973

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: 0.000722

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000274 AC: 50 AN: 182588 AF XY: 0.000238

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.0000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000626

Gnomad NFE exome AF: 0.000541

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000551 AC: 601 AN: 1091102 Hom.: 0 Cov.: 28 AF XY: 0.000496 AC XY: 177 AN XY: 356618

African (AFR) AF: 0.000114 AC: 3 AN: 26263

American (AMR) AF: 0.00 AC: 0 AN: 35157

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19328

East Asian (EAS) AF: 0.00 AC: 0 AN: 30165

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 53974

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40489

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4119

European-Non Finnish (NFE) AF: 0.000699 AC: 584 AN: 835743

Other (OTH) AF: 0.000262 AC: 12 AN: 45864

GnomAD4 genome AF: 0.000400 AC: 44 AN: 109920 Hom.: 0 Cov.: 22 AF XY: 0.000373 AC XY: 12 AN XY: 32160

African (AFR) AF: 0.000166 AC: 5 AN: 30141

American (AMR) AF: 0.0000973 AC: 1 AN: 10277

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2610

East Asian (EAS) AF: 0.00 AC: 0 AN: 3509

South Asian (SAS) AF: 0.00 AC: 0 AN: 2469

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5879

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.000722 AC: 38 AN: 52651

Other (OTH) AF: 0.00 AC: 0 AN: 1472

Alfa AF: 0.000569 Hom.: 1

Bravo AF: 0.000393

EpiCase AF: 0.000436

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	MSN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs372696816; hg19: chrX-64936770; COSMIC: COSV64304632;