Genetic Variant MOSPD1:p.Arg82Gln (chrX-134897020-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_019556.3(MOSPD1):c.245G>A(p.Arg82Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000209 in 1,197,271 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000020 ( 0 hom. 14 hem. )

Consequence

MOSPD1
NM_019556.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14605558).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019556.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOSPD1	NM_019556.3	MANE Select	c.245G>A	p.Arg82Gln	missense	Exon 4 of 6	NP_062456.1	Q9UJG1-1
	MOSPD1	NM_001306188.2		c.245G>A	p.Arg82Gln	missense	Exon 4 of 5	NP_001293117.1	Q9UJG1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOSPD1	ENST00000370783.8	TSL:1 MANE Select	c.245G>A	p.Arg82Gln	missense	Exon 4 of 6	ENSP00000359819.3	Q9UJG1-1
MOSPD1	ENST00000491609.5	TSL:1	n.320G>A		non_coding_transcript_exon	Exon 3 of 5
MOSPD1	ENST00000370777.1	TSL:5	c.245G>A	p.Arg82Gln	missense	Exon 3 of 5	ENSP00000359813.1	Q9UJG1-3

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

110942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000564

Gnomad SAS

AF:

0.000383

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000619

AC:

AN:

177843

AF XY:

0.0000636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000512

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000203

AC:

AN:

1086277

Hom.:

Cov.:

AF XY:

0.0000397

AC XY:

AN XY:

352787

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26187

American (AMR)

AF:

0.00

AC:

AN:

34507

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19174

East Asian (EAS)

AF:

0.000167

AC:

AN:

30020

South Asian (SAS)

AF:

0.000228

AC:

AN:

52558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40435

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4091

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

833661

Other (OTH)

AF:

0.0000438

AC:

AN:

45644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000270

AC:

AN:

110994

Hom.:

Cov.:

AF XY:

0.0000601

AC XY:

AN XY:

33266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30617

American (AMR)

AF:

0.00

AC:

AN:

10300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.000565

AC:

AN:

3537

South Asian (SAS)

AF:

0.000384

AC:

AN:

2601

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5835

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53055

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.7

PhyloP100

3.8

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.33

REVEL

Benign

0.24

Sift

Benign

0.43

Sift4G

Benign

0.61

Polyphen

0.71

Vest4

0.21

MutPred

0.53

Loss of MoRF binding (P = 0.0651)

MVP

0.65

MPC

1.0

ClinPred

0.070

GERP RS

4.1

Varity_R

0.22

gMVP

0.52

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over