ENST00000609205.5:n.539+5887C>T

Variant names:

• chrX-65595656-C-T
• rs1332720
• ENST00000609205.5:n.539+5887C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000609205.5(MSN):​n.539+5887C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 112,042 control chromosomes in the GnomAD database, including 7,495 homozygotes. There are 7,382 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.

• Frequency: Genomes: 𝑓 0.24 (7495 hom., 7382 hem., cov: 23)
• Consequence: MSN ENST00000609205.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 1 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: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000301275 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSN	NM_001440778.1	c.15+7044C>T		intron_variant	Intron 1 of 12		NP_001427707.1
MSN	XM_011530959.1	c.111+6588C>T		intron_variant	Intron 1 of 12		XP_011529261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSN	ENST00000609205.5	n.539+5887C>T		intron_variant	Intron 3 of 3	1
MSN	ENST00000609672.5	c.-22+7044C>T		intron_variant	Intron 1 of 3	4		ENSP00000477441.1
MSN	ENST00000429601.1	n.399-5006C>T		intron_variant	Intron 2 of 2	5
ENSG00000301275	ENST00000777606.1	n.-177G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.236 AC: 26409 AN: 111992 Hom.: 7487 Cov.: 23

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.00604

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00258

Gnomad MID AF: 0.0546

Gnomad NFE AF: 0.00514

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.236 AC: 26472 AN: 112042 Hom.: 7495 Cov.: 23 AF XY: 0.216 AC XY: 7382 AN XY: 34228

African (AFR) AF: 0.817 AC: 24927 AN: 30527

American (AMR) AF: 0.0847 AC: 900 AN: 10624

Ashkenazi Jewish (ASJ) AF: 0.00604 AC: 16 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.0188 AC: 52 AN: 2765

European-Finnish (FIN) AF: 0.00258 AC: 16 AN: 6190

Middle Eastern (MID) AF: 0.0599 AC: 13 AN: 217

European-Non Finnish (NFE) AF: 0.00515 AC: 274 AN: 53251

Other (OTH) AF: 0.178 AC: 274 AN: 1537

Alfa AF: 0.0504 Hom.: 1344

Bravo AF: 0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.83
DANN	Benign	0.68
PhyloP100		-0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1332720; hg19: chrX-64815536;