X-14918680-G-A

Position:

• chrX-14918680-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The ENST00000380492.8(MOSPD2):​c.1317G>A​(p.Arg439Arg) variant causes a splice region, synonymous 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MOSPD2 ENST00000380492.8 splice_region, synonymous
• Scores: Splicing: ADA: 0.02060
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant X-14918680-G-A is Benign according to our data. Variant chrX-14918680-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3200565.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOSPD2	NM_152581.4	c.1317G>A	p.Arg439Arg	splice_region_variant, synonymous_variant	14/15	ENST00000380492.8	NP_689794.1
MOSPD2	NM_001330241.2	c.1317G>A	p.Arg439Arg	splice_region_variant, synonymous_variant	14/15		NP_001317170.1
MOSPD2	NM_001177475.2	c.1128G>A	p.Arg376Arg	splice_region_variant, synonymous_variant	13/14		NP_001170946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOSPD2	ENST00000380492.8	c.1317G>A	p.Arg439Arg	splice_region_variant, synonymous_variant	14/15	1	NM_152581.4	ENSP00000369860.3
MOSPD2	ENST00000482354.5	c.1317G>A	p.Arg439Arg	splice_region_variant, synonymous_variant	14/15	5		ENSP00000473271.1
MOSPD2	ENST00000495110.1	n.1405G>A		splice_region_variant, non_coding_transcript_exon_variant	13/14	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.021
dbscSNV1_RF	Benign	0.41
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-14936802;