Genetic Variant NM_023948.5:c.50C>G (chr7-100612841-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023948.5(MOSPD3):c.50C>G(p.Pro17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MOSPD3
NM_023948.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.407

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1744206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOSPD3	NM_023948.5 link	c.50C>G	p.Pro17Arg	missense_variant	Exon 1 of 5	ENST00000393950.7	NP_076438.1	O75425-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOSPD3	ENST00000393950.7 link	c.50C>G	p.Pro17Arg	missense_variant	Exon 1 of 5	1	NM_023948.5	ENSP00000377522.2		O75425-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725864

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33344

American (AMR)

AF:

0.00

AC:

AN:

44254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25970

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111292

Other (OTH)

AF:

0.00

AC:

AN:

60234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 03, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.50C>G (p.P17R) alteration is located in exon 1 (coding exon 1) of the MOSPD3 gene. This alteration results from a C to G substitution at nucleotide position 50, causing the proline (P) at amino acid position 17 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

Benign

0.089

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;.;T;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.77

.;T;T;.;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.;N;N;N

PhyloP100

0.41

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.28

N;N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.040

D;D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D;D

Polyphen

0.74

P;.;P;P;.

Vest4

0.29

MutPred

0.24

Gain of methylation at P17 (P = 0.0085);Gain of methylation at P17 (P = 0.0085);Gain of methylation at P17 (P = 0.0085);Gain of methylation at P17 (P = 0.0085);Gain of methylation at P17 (P = 0.0085);

MVP

0.36

MPC

0.74

ClinPred

0.34

GERP RS

2.3

PromoterAI

-0.029

Neutral

(source)

Varity_R

0.072

gMVP

0.25

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over