Genetic Variant NM_018995.3:c.2383C>T (chr22-50144121-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018995.3(MOV10L1):c.2383C>T(p.Arg795Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,458,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R795Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MOV10L1
NM_018995.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.55

Publications

22 publications found

Variant links:

Genes affected

MOV10L1 (HGNC:7201): (Mov10 like RNA helicase 1) This gene is similar to a mouse gene that encodes a putative RNA helicase and shows testis-specific expression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

MOV10L1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.927

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018995.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MOV10L1	NM_018995.3	MANE Select	c.2383C>T	p.Arg795Trp	missense	Exon 18 of 27	NP_061868.1
MOV10L1	NM_001164104.2		c.2383C>T	p.Arg795Trp	missense	Exon 18 of 26	NP_001157576.1
MOV10L1	NM_001164105.2		c.2323C>T	p.Arg775Trp	missense	Exon 18 of 26	NP_001157577.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MOV10L1	ENST00000262794.10	TSL:1 MANE Select	c.2383C>T	p.Arg795Trp	missense	Exon 18 of 27	ENSP00000262794.5
MOV10L1	ENST00000395858.7	TSL:1	c.2383C>T	p.Arg795Trp	missense	Exon 18 of 26	ENSP00000379199.3
MOV10L1	ENST00000540615.5	TSL:2	c.2323C>T	p.Arg775Trp	missense	Exon 18 of 26	ENSP00000438542.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251206

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458036

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724538

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.0000895

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.00

AC:

AN:

86122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1108812

Other (OTH)

AF:

0.00

AC:

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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

Cov.:

Alfa

AF:

0.00

Hom.:

4014

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.88

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.93

MetaSVM

Pathogenic

0.88

MutationAssessor

Pathogenic

3.9

PhyloP100

4.6

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.0

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.92

MutPred

0.62

Gain of loop (P = 0.069)

MVP

0.94

MPC

0.49

ClinPred

1.0

GERP RS

4.8

Varity_R

0.87

gMVP

0.84

Mutation Taster

=183/117

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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