X-14911267-G-A

Position:

• chrX-14911267-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152581.4(MOSPD2):​c.733G>A​(p.Val245Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MOSPD2 NM_152581.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2076217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOSPD2	NM_152581.4	c.733G>A	p.Val245Ile	missense_variant	9/15	ENST00000380492.8	NP_689794.1
MOSPD2	NM_001330241.2	c.733G>A	p.Val245Ile	missense_variant	9/15		NP_001317170.1
MOSPD2	NM_001177475.2	c.544G>A	p.Val182Ile	missense_variant	8/14		NP_001170946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOSPD2	ENST00000380492.8	c.733G>A	p.Val245Ile	missense_variant	9/15	1	NM_152581.4	ENSP00000369860.3
MOSPD2	ENST00000482354.5	c.733G>A	p.Val245Ile	missense_variant	9/15	5		ENSP00000473271.1
MOSPD2	ENST00000460386.1	c.94G>A	p.Val32Ile	missense_variant	2/5	5		ENSP00000473379.1
MOSPD2	ENST00000495110.1	n.821G>A		non_coding_transcript_exon_variant	8/14	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

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

Feb 22, 2023

The c.733G>A (p.V245I) alteration is located in exon 9 (coding exon 9) of the MOSPD2 gene. This alteration results from a G to A substitution at nucleotide position 733, causing the valine (V) at amino acid position 245 to be replaced by an isoleucine (I). 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	0.098
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;T;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.56	N;.;.
REVEL	Benign	0.19
Sift	Benign	0.44	T;.;.
Sift4G	Benign	0.46	T;T;T
Polyphen		0.98	D;.;.
Vest4		0.074
MVP		0.73
MPC		0.46
ClinPred		0.56	D
GERP RS		3.2
Varity_R		0.069
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs370959017; hg19: chrX-14929389;