Genetic Variant MX1:p.Ala541Ala (chr21-41452734-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002462.5(MX1):c.1623A>G(p.Ala541Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,964 control chromosomes in the GnomAD database, including 25,808 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3166 hom., cov: 32)

Exomes 𝑓: 0.16 ( 22642 hom. )

Consequence

MX1
NM_002462.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.40

Publications

23 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-5.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5 link	c.1623A>G	p.Ala541Ala	synonymous_variant	Exon 16 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.1623A>G	p.Ala541Ala	synonymous_variant	Exon 16 of 17	1	NM_002462.5	ENSP00000381599.3		P20591-1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28563

AN:

152004

Hom.:

3156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.0853

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.206

AC:

51753

AN:

251430

AF XY:

0.205

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.160

AC:

233470

AN:

1461842

Hom.:

22642

Cov.:

AF XY:

0.163

AC XY:

118520

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.240

AC:

8026

AN:

33476

American (AMR)

AF:

0.232

AC:

10371

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0910

AC:

2379

AN:

26136

East Asian (EAS)

AF:

0.455

AC:

18082

AN:

39700

South Asian (SAS)

AF:

0.289

AC:

24890

AN:

86256

European-Finnish (FIN)

AF:

0.210

AC:

11204

AN:

53418

Middle Eastern (MID)

AF:

0.162

AC:

936

AN:

5768

European-Non Finnish (NFE)

AF:

0.132

AC:

147116

AN:

1111970

Other (OTH)

AF:

0.173

AC:

10466

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11324

22648

33973

45297

56621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5554

11108

16662

22216

27770

<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:

0.188

AC:

28608

AN:

152122

Hom.:

3166

Cov.:

AF XY:

0.196

AC XY:

14551

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.235

AC:

9746

AN:

41500

American (AMR)

AF:

0.161

AC:

2459

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0853

AC:

296

AN:

3472

East Asian (EAS)

AF:

0.464

AC:

2395

AN:

5164

South Asian (SAS)

AF:

0.296

AC:

1425

AN:

4814

European-Finnish (FIN)

AF:

0.214

AC:

2264

AN:

10586

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.139

AC:

9477

AN:

67992

Other (OTH)

AF:

0.168

AC:

355

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1149

2298

3448

4597

5746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.155

Hom.:

7485

Bravo

AF:

0.187

Asia WGS

AF:

0.376

AC:

1310

AN:

3478

EpiCase

AF:

0.135

EpiControl

AF:

0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.037

(source)

DANN

Benign

0.31

PhyloP100

-5.4

Mutation Taster

=100/0

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