Genetic Variant MOV10:p.Arg32Ser (chr1-112675006-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_001321324.2(MOV10):c.94C>A(p.Arg32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000272 in 1,583,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MOV10
NM_001321324.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Publications

1 publications found

Variant links:

Genes affected

MOV10 (HGNC:7200): (Mov10 RNA helicase) Enables 5'-3' RNA helicase activity and RNA binding activity. Involved in defense response to virus; negative regulation of transposition, RNA-mediated; and posttranscriptional regulation of gene expression. Located in P-body and cytosol. Implicated in hypertension. [provided by Alliance of Genome Resources, Apr 2022]

MOV10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.774

BS2

High AC in GnomAdExome4 at 41 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321324.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOV10	NM_001321324.2	MANE Select	c.94C>A	p.Arg32Ser	missense	Exon 2 of 21	NP_001308253.1	Q9HCE1-1
MOV10	NM_001130079.3		c.94C>A	p.Arg32Ser	missense	Exon 2 of 21	NP_001123551.1	Q9HCE1-1
MOV10	NM_001369507.1		c.94C>A	p.Arg32Ser	missense	Exon 1 of 20	NP_001356436.1	Q9HCE1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOV10	ENST00000369645.6	TSL:5 MANE Select	c.94C>A	p.Arg32Ser	missense	Exon 2 of 21	ENSP00000358659.1	Q9HCE1-1
MOV10	ENST00000357443.2	TSL:1	c.94C>A	p.Arg32Ser	missense	Exon 1 of 20	ENSP00000350028.2	Q9HCE1-1
MOV10	ENST00000413052.6	TSL:1	c.94C>A	p.Arg32Ser	missense	Exon 2 of 21	ENSP00000399797.2	Q9HCE1-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152156

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000182

AC:

AN:

219810

AF XY:

0.0000167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000300

Gnomad OTH exome

AF:

0.000197

GnomAD4 exome

AF:

0.0000286

AC:

AN:

1431500

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

711908

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30572

American (AMR)

AF:

0.00

AC:

AN:

41130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25302

East Asian (EAS)

AF:

0.00

AC:

AN:

34988

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000355

AC:

AN:

1098082

Other (OTH)

AF:

0.0000169

AC:

AN:

59164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203476), 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

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Benign

0.053

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.90

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

1.7

PhyloP100

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.8

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.033

Polyphen

1.0

Vest4

0.67

MutPred

0.52

Loss of helix (P = 0.0444)

MVP

0.91

MPC

2.5

ClinPred

0.88

GERP RS

3.5

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.66

Mutation Taster

=74/26

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over