Variant X-14919694-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152581.4(MOSPD2):c.1442A>G(p.Asn481Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,094,986 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MOSPD2
NM_152581.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.096785694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MOSPD2	NM_152581.4 linkuse as main transcript	c.1442A>G	p.Asn481Ser	missense_variant	15/15	ENST00000380492.8	NP_689794.1
MOSPD2	NM_001177475.2 linkuse as main transcript	c.1253A>G	p.Asn418Ser	missense_variant	14/14		NP_001170946.1
MOSPD2	NM_001330241.2 linkuse as main transcript	c.1419+912A>G		intron_variant			NP_001317170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOSPD2	ENST00000380492.8 linkuse as main transcript	c.1442A>G	p.Asn481Ser	missense_variant	15/15	1	NM_152581.4	ENSP00000369860	P1	Q8NHP6-1
MOSPD2	ENST00000482354.5 linkuse as main transcript	c.1419+912A>G		intron_variant		5		ENSP00000473271
MOSPD2	ENST00000495110.1 linkuse as main transcript	n.1530A>G		non_coding_transcript_exon_variant	14/14	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

112450

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34602

FAILED QC

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000558

AC:

AN:

179226

Hom.:

AF XY:

0.00

AC XY:

AN XY:

64044

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.13e-7

AC:

AN:

1094986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

360608

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000889

AC:

AN:

112450

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34602

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 29, 2024

The c.1442A>G (p.N481S) alteration is located in exon 15 (coding exon 15) of the MOSPD2 gene. This alteration results from a A to G substitution at nucleotide position 1442, causing the asparagine (N) at amino acid position 481 to be replaced by a serine (S). 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

0.064

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.031

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.73

M_CAP

Benign

0.021

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.6

REVEL

Benign

0.14

Sift

Benign

0.30

Sift4G

Pathogenic

0.0

Polyphen

0.11

Vest4

0.096

MutPred

0.45

Loss of helix (P = 0.0237);

MVP

0.73

MPC

0.46

ClinPred

0.078

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over