Variant X-14912325-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152581.4(MOSPD2):c.956C>G(p.Pro319Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,172,469 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 56 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. 48 hem. )

Consequence

MOSPD2
NM_152581.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12258494).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MOSPD2	NM_152581.4 linkuse as main transcript	c.956C>G	p.Pro319Arg	missense_variant	10/15	ENST00000380492.8	NP_689794.1
MOSPD2	NM_001330241.2 linkuse as main transcript	c.956C>G	p.Pro319Arg	missense_variant	10/15		NP_001317170.1
MOSPD2	NM_001177475.2 linkuse as main transcript	c.767C>G	p.Pro256Arg	missense_variant	9/14		NP_001170946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOSPD2	ENST00000380492.8 linkuse as main transcript	c.956C>G	p.Pro319Arg	missense_variant	10/15	1	NM_152581.4	ENSP00000369860	P1	Q8NHP6-1
MOSPD2	ENST00000482354.5 linkuse as main transcript	c.956C>G	p.Pro319Arg	missense_variant	10/15	5		ENSP00000473271
MOSPD2	ENST00000460386.1 linkuse as main transcript	c.317C>G	p.Pro106Arg	missense_variant	3/5	5		ENSP00000473379
MOSPD2	ENST00000495110.1 linkuse as main transcript	n.1044C>G		non_coding_transcript_exon_variant	9/14	2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

110993

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

33313

show subpopulations

Gnomad AFR

AF:

0.0000654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000192

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:

0.000246

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.000115

AC:

AN:

156272

Hom.:

AF XY:

0.000201

AC XY:

AN XY:

49638

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000234

Gnomad OTH exome

AF:

0.000277

GnomAD4 exome

AF:

0.000125

AC:

133

AN:

1061430

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

337882

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000544

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000203

GnomAD4 genome

AF:

0.000171

AC:

AN:

111039

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

AN XY:

33369

show subpopulations

Gnomad4 AFR

AF:

0.0000653

Gnomad4 AMR

AF:

0.000192

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000246

Gnomad4 OTH

AF:

0.00133

Bravo

AF:

0.000144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000181

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

May 16, 2023

The c.956C>G (p.P319R) alteration is located in exon 10 (coding exon 10) of the MOSPD2 gene. This alteration results from a C to G substitution at nucleotide position 956, causing the proline (P) at amino acid position 319 to be replaced by an arginine (R). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

T;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

N;.;.

REVEL

Benign

0.14

Sift

Uncertain

0.011

D;.;.

Sift4G

Uncertain

0.025

D;T;D

Polyphen

0.96

P;.;.

Vest4

0.11

MVP

0.47

MPC

0.88

ClinPred

0.18

GERP RS

4.8

Varity_R

0.66

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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