dbSNP rs464138: MX1:c.-326A>C (chr21-41426246-A-C) – 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.-326A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 153,632 control chromosomes in the GnomAD database, including 11,183 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 0.36 ( 11030 hom., cov: 33)

Exomes 𝑓: 0.46 ( 153 hom. )

Consequence

MX1
NM_002462.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.34

Publications

14 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 (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5 link	c.-326A>C		5_prime_UTR_variant	Exon 1 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.-326A>C		5_prime_UTR_variant	Exon 1 of 17	1	NM_002462.5	ENSP00000381599.3		P20591-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55227

AN:

152022

Hom.:

11036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.392

GnomAD4 exome

AF:

0.457

AC:

682

AN:

1492

Hom.:

153

Cov.:

AF XY:

0.452

AC XY:

392

AN XY:

868

show subpopulations

African (AFR)

AF:

0.292

AC:

AN:

American (AMR)

AF:

0.563

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

AN:

East Asian (EAS)

AF:

0.639

AC:

AN:

122

South Asian (SAS)

AF:

0.200

AC:

AN:

European-Finnish (FIN)

AF:

0.427

AC:

AN:

124

Middle Eastern (MID)

AF:

0.600

AC:

AN:

European-Non Finnish (NFE)

AF:

0.441

AC:

467

AN:

1058

Other (OTH)

AF:

0.544

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.363

AC:

55230

AN:

152140

Hom.:

11030

Cov.:

AF XY:

0.368

AC XY:

27381

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.193

AC:

8014

AN:

41538

American (AMR)

AF:

0.454

AC:

6951

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1672

AN:

3472

East Asian (EAS)

AF:

0.582

AC:

2989

AN:

5138

South Asian (SAS)

AF:

0.363

AC:

1749

AN:

4824

European-Finnish (FIN)

AF:

0.453

AC:

4800

AN:

10590

Middle Eastern (MID)

AF:

0.473

AC:

138

AN:

292

European-Non Finnish (NFE)

AF:

0.409

AC:

27794

AN:

67966

Other (OTH)

AF:

0.392

AC:

827

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1808

3617

5425

7234

9042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.352

Hom.:

4559

Bravo

AF:

0.360

Asia WGS

AF:

0.460

AC:

1596

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.3

(source)

DANN

Benign

0.29

PhyloP100

-6.3

PromoterAI

-0.21

Neutral

(source)

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