dbSNP rs467960: MX1:p.Ile223Ile (chr21-41440964-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_002462.5(MX1):c.669C>T(p.Ile223Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,613,894 control chromosomes in the GnomAD database, including 245,356 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 0.48 ( 18738 hom., cov: 32)

Exomes 𝑓: 0.55 ( 226618 hom. )

Consequence

MX1
NM_002462.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

Publications

21 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:

MX1-AS1 (HGNC:40383):

MX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP7

Synonymous conserved (PhyloP=-2.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5 link	c.669C>T	p.Ile223Ile	synonymous_variant	Exon 9 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.669C>T	p.Ile223Ile	synonymous_variant	Exon 9 of 17	1	NM_002462.5	ENSP00000381599.3		P20591-1

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72842

AN:

151988

Hom.:

18725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.723

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.498

GnomAD2 exomes

AF:

0.466

AC:

117190

AN:

251410

AF XY:

0.472

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.516

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.482

GnomAD4 exome

AF:

0.546

AC:

798279

AN:

1461788

Hom.:

226618

Cov.:

AF XY:

0.542

AC XY:

393895

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.344

AC:

11503

AN:

33478

American (AMR)

AF:

0.391

AC:

17495

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

11612

AN:

26132

East Asian (EAS)

AF:

0.0897

AC:

3561

AN:

39698

South Asian (SAS)

AF:

0.373

AC:

32156

AN:

86258

European-Finnish (FIN)

AF:

0.516

AC:

27545

AN:

53406

Middle Eastern (MID)

AF:

0.462

AC:

2664

AN:

5764

European-Non Finnish (NFE)

AF:

0.595

AC:

661198

AN:

1111938

Other (OTH)

AF:

0.506

AC:

30545

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

20037

40074

60111

80148

100185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17702

35404

53106

70808

88510

<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:

0.479

AC:

72905

AN:

152106

Hom.:

18738

Cov.:

AF XY:

0.471

AC XY:

34994

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.351

AC:

14566

AN:

41502

American (AMR)

AF:

0.472

AC:

7225

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1551

AN:

3472

East Asian (EAS)

AF:

0.102

AC:

528

AN:

5164

South Asian (SAS)

AF:

0.367

AC:

1767

AN:

4816

European-Finnish (FIN)

AF:

0.503

AC:

5321

AN:

10586

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40105

AN:

67954

Other (OTH)

AF:

0.497

AC:

1050

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1872

3744

5616

7488

9360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.538

Hom.:

19955

Bravo

AF:

0.469

Asia WGS

AF:

0.248

AC:

865

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

6.5

(source)

DANN

Benign

0.83

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(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

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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