Genetic Variant MOSPD1:p.Lys111Arg (chrX-134896933-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

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

The NM_019556.3(MOSPD1):c.332A>G(p.Lys111Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000803 in 1,208,486 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 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 0.000081 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000080 ( 0 hom. 26 hem. )

Consequence

MOSPD1
NM_019556.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18031493).

BS2

High Hemizygotes in GnomAdExome4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOSPD1	NM_019556.3 link	c.332A>G	p.Lys111Arg	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.332A>G	p.Lys111Arg	missense_variant	Exon 4 of 6	1	NM_019556.3	ENSP00000359819.3		Q9UJG1-1

Frequencies

GnomAD3 genomes

AF:

0.0000805

AC:

AN:

111751

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33919

show subpopulations

Gnomad AFR

AF:

0.000130

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:

0.0000939

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

183303

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67781

show subpopulations

Gnomad AFR exome

AF:

0.000304

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:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000802

AC:

AN:

1096735

Hom.:

Cov.:

AF XY:

0.0000718

AC XY:

AN XY:

362129

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.000103

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000805

AC:

AN:

111751

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33919

show subpopulations

Gnomad4 AFR

AF:

0.000130

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:

0.0000939

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332A>G (p.K111R) alteration is located in exon 4 (coding exon 3) of the MOSPD1 gene. This alteration results from a A to G substitution at nucleotide position 332, causing the lysine (K) at amino acid position 111 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

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.51

T;T;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.58

P;P;.

Vest4

0.58

MVP

0.63

MPC

1.0

ClinPred

0.12

GERP RS

4.8

Varity_R

0.22

gMVP

0.63

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