dbSNP rs469390: MX1:p.Val379Ile (chr21-41446003-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002462.5(MX1):c.1135G>A(p.Val379Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,612,458 control chromosomes in the GnomAD database, including 265,268 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 21625 hom., cov: 32)

Exomes 𝑓: 0.57 ( 243643 hom. )

Consequence

MX1
NM_002462.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

Publications

71 publications found

Variant links:

Genes affected

MX1 (HGNC:7532): (MX dynamin like GTPase 1) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that participates in the cellular antiviral response. The encoded protein is induced by type I and type II interferons and antagonizes the replication process of several different RNA and DNA viruses. There is a related gene located adjacent to this gene on chromosome 21, and there are multiple pseudogenes located in a cluster on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MX1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1764186E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5 link	c.1135G>A	p.Val379Ile	missense_variant	Exon 13 of 17	ENST00000398598.8	NP_002453.2	P20591-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8 link	c.1135G>A	p.Val379Ile	missense_variant	Exon 13 of 17	1	NM_002462.5	ENSP00000381599.3		P20591-1

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79891

AN:

151912

Hom.:

21603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.723

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.529

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.533

GnomAD2 exomes

AF:

0.514

AC:

128953

AN:

250946

AF XY:

0.523

show subpopulations

Gnomad AFR exome

AF:

0.445

Gnomad AMR exome

AF:

0.394

Gnomad ASJ exome

AF:

0.477

Gnomad EAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.532

Gnomad NFE exome

AF:

0.596

Gnomad OTH exome

AF:

0.514

GnomAD4 exome

AF:

0.572

AC:

835897

AN:

1460428

Hom.:

243643

Cov.:

AF XY:

0.572

AC XY:

415200

AN XY:

726376

show subpopulations

African (AFR)

AF:

0.441

AC:

14749

AN:

33460

American (AMR)

AF:

0.404

AC:

18039

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

12299

AN:

26114

East Asian (EAS)

AF:

0.226

AC:

8955

AN:

39680

South Asian (SAS)

AF:

0.530

AC:

45648

AN:

86162

European-Finnish (FIN)

AF:

0.533

AC:

28434

AN:

53392

Middle Eastern (MID)

AF:

0.508

AC:

2926

AN:

5762

European-Non Finnish (NFE)

AF:

0.605

AC:

672014

AN:

1110856

Other (OTH)

AF:

0.544

AC:

32833

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16469

32938

49407

65876

82345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18036

36072

54108

72144

90180

<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:

0.526

AC:

79962

AN:

152030

Hom.:

21625

Cov.:

AF XY:

0.520

AC XY:

38650

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.450

AC:

18649

AN:

41440

American (AMR)

AF:

0.488

AC:

7453

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

1646

AN:

3470

East Asian (EAS)

AF:

0.263

AC:

1363

AN:

5184

South Asian (SAS)

AF:

0.529

AC:

2548

AN:

4816

European-Finnish (FIN)

AF:

0.518

AC:

5466

AN:

10554

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.602

AC:

40917

AN:

67976

Other (OTH)

AF:

0.535

AC:

1128

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1910

3820

5731

7641

9551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.562

Hom.:

99711

Bravo

AF:

0.515

TwinsUK

AF:

0.598

AC:

2217

ALSPAC

AF:

0.603

AC:

2325

ESP6500AA

AF:

0.448

AC:

1976

ESP6500EA

AF:

0.589

AC:

5065

ExAC

AF:

0.517

AC:

62765

Asia WGS

AF:

0.414

AC:

1442

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.2

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.19

T;T;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.46

.;T;.;T;T

MetaRNN

Benign

0.000022

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.7

N;N;N;.;N

PhyloP100

1.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.58

N;N;N;N;.

REVEL

Benign

0.058

Sift

Benign

1.0

T;T;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;B;.;.

Vest4

0.027

MPC

0.086

ClinPred

0.00054

GERP RS

2.3

Varity_R

0.067

gMVP

0.11

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over