Variant 7-100613268-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023948.5(MOSPD3):c.280A>G(p.Ile94Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000491 in 1,424,250 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

MOSPD3
NM_023948.5 missense, splice_region

Scores

Splicing: ADA: 0.9755

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOSPD3	NM_023948.5 linkuse as main transcript	c.280A>G	p.Ile94Val	missense_variant, splice_region_variant	2/5	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.280A>G	p.Ile94Val	missense_variant, splice_region_variant	2/5	1	NM_023948.5	ENSP00000377522.2		O75425-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251396

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00000491

AC:

AN:

1424250

Hom.:

Cov.:

AF XY:

0.00000423

AC XY:

AN XY:

709060

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

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

Oct 16, 2024

The c.280A>G (p.I94V) alteration is located in exon 2 (coding exon 2) of the MOSPD3 gene. This alteration results from a A to G substitution at nucleotide position 280, causing the isoleucine (I) at amino acid position 94 to be replaced by a valine (V). 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

0.32

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;.;T;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.059

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

.;T;D;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.38

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

L;.;L;L;L

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.90

N;N;N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0060

D;D;D;D;D

Sift4G

Benign

0.077

T;T;T;T;D

Polyphen

0.0

B;.;B;B;.

Vest4

0.48

MutPred

0.75

Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);

MVP

0.69

MPC

0.26

ClinPred

0.58

GERP RS

3.8

Varity_R

0.17

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.79

SpliceAI score (max)

0.14

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