X-14897125-A-T

Position:

• chrX-14897125-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000380492.8(MOSPD2):​c.364A>T​(p.Ile122Leu) 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 benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MOSPD2 ENST00000380492.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

Genes affected

MOSPD2 (HGNC:28381): (motile sperm domain containing 2) Involved in positive regulation of monocyte chemotaxis and positive regulation of neutrophil chemotaxis. Located in endoplasmic reticulum and endoplasmic reticulum-endosome membrane contact site. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MOSPD2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039574087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOSPD2	NM_152581.4	c.364A>T	p.Ile122Leu	missense_variant	5/15	ENST00000380492.8	NP_689794.1
MOSPD2	NM_001330241.2	c.364A>T	p.Ile122Leu	missense_variant	5/15		NP_001317170.1
MOSPD2	NM_001177475.2	c.175A>T	p.Ile59Leu	missense_variant	4/14		NP_001170946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOSPD2	ENST00000380492.8	c.364A>T	p.Ile122Leu	missense_variant	5/15	1	NM_152581.4	ENSP00000369860.3
MOSPD2	ENST00000482354.5	c.364A>T	p.Ile122Leu	missense_variant	5/15	5		ENSP00000473271.1
MOSPD2	ENST00000495110.1	n.452A>T		non_coding_transcript_exon_variant	4/14	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.364A>T (p.I122L) alteration is located in exon 5 (coding exon 5) of the MOSPD2 gene. This alteration results from a A to T substitution at nucleotide position 364, causing the isoleucine (I) at amino acid position 122 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.9
DANN	Benign	0.73
DEOGEN2	Benign	0.095	T;T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.45	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.27	N;.
REVEL	Benign	0.058
Sift	Benign	0.64	T;.
Sift4G	Benign	0.65	T;T
Polyphen		0.0010	B;.
Vest4		0.14
MutPred		0.29		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP		0.21
MPC		0.56
ClinPred		0.022	T
GERP RS		1.3
Varity_R		0.068
gMVP		0.77

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

Other links and lift over

dbSNP: rs930032726; hg19: chrX-14915247;