Variant 7-100613526-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_023948.5(MOSPD3):c.331C>A(p.Arg111Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

MOSPD3
NM_023948.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

MOSPD3 (HGNC:25078): (motile sperm domain containing 3) This gene encodes a multi-pass membrane protein with a major sperm protein (MSP) domain. The deletion of a similar mouse gene is associated with defective cardiac development and neonatal lethality. Alternate transcriptional splice variants, encoding different isoforms, have been described. [provided by RefSeq, Jul 2008]

MOSPD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32180694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOSPD3	NM_023948.5 linkuse as main transcript	c.331C>A	p.Arg111Ser	missense_variant	3/5	ENST00000393950.7	NP_076438.1	O75425-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOSPD3	ENST00000393950.7 linkuse as main transcript	c.331C>A	p.Arg111Ser	missense_variant	3/5	1	NM_023948.5	ENSP00000377522.2		O75425-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000187

AC:

AN:

251478

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000338

AC:

494

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

253

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.000400

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000197

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000331

Hom.:

Bravo

AF:

0.000230

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000652

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

Dec 10, 2024

The c.331C>A (p.R111S) alteration is located in exon 3 (coding exon 3) of the MOSPD3 gene. This alteration results from a C to A substitution at nucleotide position 331, causing the arginine (R) at amino acid position 111 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

Pathogenic

0.66

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

D;.;D;D;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.72

.;T;T;.;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.32

T;T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.55

N;.;N;N;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Uncertain

0.51

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

0.99

D;.;D;D;.

Vest4

0.80

MutPred

0.70

Gain of phosphorylation at R111 (P = 0.0635);Gain of phosphorylation at R111 (P = 0.0635);Gain of phosphorylation at R111 (P = 0.0635);Gain of phosphorylation at R111 (P = 0.0635);.;

MVP

0.81

MPC

0.98

ClinPred

0.078

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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