Variant chrX-14918736-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000380492.8(MOSPD2):c.1373A>G(p.Asn458Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000061 in 1,197,221 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. 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: 𝑓 0.000089 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000058 ( 0 hom. 16 hem. )

Consequence

MOSPD2
ENST00000380492.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500

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:

MOSPD2 (HGNC:):

MOSPD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032533556).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOSPD2	NM_152581.4 linkuse as main transcript	c.1373A>G	p.Asn458Ser	missense_variant	14/15	ENST00000380492.8	NP_689794.1	Q8NHP6-1
MOSPD2	NM_001330241.2 linkuse as main transcript	c.1373A>G	p.Asn458Ser	missense_variant	14/15		NP_001317170.1	R4GMN1
MOSPD2	NM_001177475.2 linkuse as main transcript	c.1184A>G	p.Asn395Ser	missense_variant	13/14		NP_001170946.1	Q8NHP6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MOSPD2	ENST00000380492.8 linkuse as main transcript	c.1373A>G	p.Asn458Ser	missense_variant	14/15	1	NM_152581.4	ENSP00000369860.3	Q8NHP6-1
MOSPD2	ENST00000482354.5 linkuse as main transcript	c.1373A>G	p.Asn458Ser	missense_variant	14/15	5		ENSP00000473271.1	R4GMN1
MOSPD2	ENST00000495110.1 linkuse as main transcript	n.1461A>G		non_coding_transcript_exon_variant	13/14	2

Frequencies

GnomAD3 genomes

AF:

0.0000886

AC:

AN:

112813

Hom.:

Cov.:

AF XY:

0.0000858

AC XY:

AN XY:

34947

show subpopulations

Gnomad AFR

AF:

0.0000322

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:

0.000169

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000331

AC:

AN:

181141

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

65911

show subpopulations

Gnomad AFR exome

AF:

0.0000766

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000534

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000493

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000581

AC:

AN:

1084408

Hom.:

Cov.:

AF XY:

0.0000456

AC XY:

AN XY:

350614

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.0000494

Gnomad4 NFE exome

AF:

0.0000663

Gnomad4 OTH exome

AF:

0.0000439

GnomAD4 genome

AF:

0.0000886

AC:

AN:

112813

Hom.:

Cov.:

AF XY:

0.0000858

AC XY:

AN XY:

34947

show subpopulations

Gnomad4 AFR

AF:

0.0000322

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:

0.000169

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

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

Mar 16, 2022

The c.1373A>G (p.N458S) alteration is located in exon 14 (coding exon 14) of the MOSPD2 gene. This alteration results from a A to G substitution at nucleotide position 1373, causing the asparagine (N) at amino acid position 458 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

0.053

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

DANN

Benign

0.36

DEOGEN2

Benign

0.013

T;T

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.47

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.90

N;.

REVEL

Benign

0.14

Sift

Benign

0.40

T;.

Sift4G

Benign

0.24

T;T

Polyphen

0.0010

B;.

Vest4

0.0060

MutPred

0.20

Gain of phosphorylation at N458 (P = 0.0693);Gain of phosphorylation at N458 (P = 0.0693);

MVP

0.53

MPC

0.45

ClinPred

0.0092

GERP RS

-6.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.042

gMVP

0.081

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

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