Genetic Variant MOSPD1:p.Arg85Gly (chrX-134897012-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_019556.3(MOSPD1):c.253C>G(p.Arg85Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,199,209 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

MOSPD1
NM_019556.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.46

Variant links:

Genes affected

MOSPD1 (HGNC:25235): (motile sperm domain containing 1) Predicted to be involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus and perinuclear region of cytoplasm. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MOSPD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOSPD1	NM_019556.3 link	c.253C>G	p.Arg85Gly	missense_variant	Exon 4 of 6	ENST00000370783.8	NP_062456.1	Q9UJG1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOSPD1	ENST00000370783.8 link	c.253C>G	p.Arg85Gly	missense_variant	Exon 4 of 6	1	NM_019556.3	ENSP00000359819.3		Q9UJG1-1

Frequencies

GnomAD3 genomes

AF:

0.00000900

AC:

AN:

111077

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33275

show subpopulations

Gnomad AFR

AF:

0.0000327

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1088132

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

354194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000289

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

AF:

0.00000900

AC:

AN:

111077

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33275

show subpopulations

Gnomad4 AFR

AF:

0.0000327

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.253C>G (p.R85G) alteration is located in exon 4 (coding exon 3) of the MOSPD1 gene. This alteration results from a C to G substitution at nucleotide position 253, causing the arginine (R) at amino acid position 85 to be replaced by a glycine (G). 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

0.45

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Pathogenic

0.71

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.6

L;L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.4

N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.43

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.069

B;D;.

Vest4

0.45

MutPred

0.45

Loss of MoRF binding (P = 0.0298);Loss of MoRF binding (P = 0.0298);Loss of MoRF binding (P = 0.0298);

MVP

0.84

MPC

0.93

ClinPred

0.83

GERP RS

5.8

Varity_R

0.55

gMVP

0.57

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