Genetic Variant NM_019556.3:c.332A>G (chrX-134896933-T-C) – 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.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. 12/21 in silico tools predict 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

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:

Genome browser will be placed here

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=0.18031493).

BS2

High Hemizygotes in GnomAdExome4 at 26 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.332A>G	p.Lys111Arg	missense	Exon 4 of 6	NP_062456.1	Q9UJG1-1
	MOSPD1	NM_001306188.2		c.332A>G	p.Lys111Arg	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.332A>G	p.Lys111Arg	missense	Exon 4 of 6	ENSP00000359819.3	Q9UJG1-1
MOSPD1	ENST00000491609.5	TSL:1	n.407A>G		non_coding_transcript_exon	Exon 3 of 5
MOSPD1	ENST00000370777.1	TSL:5	c.332A>G	p.Lys111Arg	missense	Exon 3 of 5	ENSP00000359813.1	Q9UJG1-3

Frequencies

GnomAD3 genomes

AF:

0.0000805

AC:

AN:

111751

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000382

AC:

AN:

183303

AF XY:

0.0000148

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 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

African (AFR)

AF:

0.00

AC:

AN:

26372

American (AMR)

AF:

0.00

AC:

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19374

East Asian (EAS)

AF:

0.00

AC:

AN:

30194

South Asian (SAS)

AF:

0.00

AC:

AN:

54101

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

840776

Other (OTH)

AF:

0.0000217

AC:

AN:

46050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000805

AC:

AN:

111751

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33919

show subpopulations

African (AFR)

AF:

0.000130

AC:

AN:

30762

American (AMR)

AF:

0.00

AC:

AN:

10417

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3565

South Asian (SAS)

AF:

0.00

AC:

AN:

2647

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000939

AC:

AN:

53244

Other (OTH)

AF:

0.00

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0000683

Hom.:

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

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

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.2

PhyloP100

7.6

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.17

REVEL

Benign

0.16

Sift

Benign

0.51

Sift4G

Benign

0.45

Polyphen

0.58

Vest4

0.58

MVP

0.63

MPC

1.0

ClinPred

0.12

GERP RS

4.8

Varity_R

0.22

gMVP

0.63

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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