dbSNP rs2071430: MX1:c.-259G>T (chr21-41426138-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000455164.6(MX1):c.-259G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 170,630 control chromosomes in the GnomAD database, including 2,287 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 0.15 ( 2146 hom., cov: 33)

Exomes 𝑓: 0.12 ( 141 hom. )

Consequence

MX1
ENST00000455164.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0560

Publications

61 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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new If you want to explore the variant's impact on the transcript ENST00000455164.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000455164.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MX1	NM_001144925.2		c.-308-1068G>T	intron	N/A	NP_001138397.1	P20591-1
MX1	NM_002462.5	MANE Select	c.-434G>T	upstream_gene	N/A	NP_002453.2	P20591-1
MX1	NM_001178046.3		c.-259G>T	upstream_gene	N/A	NP_001171517.1	P20591-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MX1	ENST00000455164.6	TSL:1	c.-259G>T	5_prime_UTR	Exon 1 of 15	ENSP00000410523.2	P20591-1
MX1	ENST00000419044.6	TSL:3	c.-332G>T	5_prime_UTR	Exon 1 of 17	ENSP00000392151.2	P20591-1
MX1	ENST00000679705.1		c.-351G>T	5_prime_UTR	Exon 1 of 17	ENSP00000506372.1	P20591-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23371

AN:

152154

Hom.:

2147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0997

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.0892

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.117

AC:

2152

AN:

18358

Hom.:

141

Cov.:

AF XY:

0.115

AC XY:

1092

AN XY:

9458

show subpopulations

African (AFR)

AF:

0.193

AC:

AN:

436

American (AMR)

AF:

0.105

AC:

AN:

344

Ashkenazi Jewish (ASJ)

AF:

0.0891

AC:

AN:

550

East Asian (EAS)

AF:

0.247

AC:

495

AN:

2004

South Asian (SAS)

AF:

0.343

AC:

AN:

140

European-Finnish (FIN)

AF:

0.0923

AC:

201

AN:

2178

Middle Eastern (MID)

AF:

0.110

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0975

AC:

1131

AN:

11600

Other (OTH)

AF:

0.0967

AC:

AN:

1024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

169

253

338

422

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:

0.154

AC:

23392

AN:

152272

Hom.:

2146

Cov.:

AF XY:

0.155

AC XY:

11529

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.209

AC:

8685

AN:

41552

American (AMR)

AF:

0.115

AC:

1763

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0997

AC:

346

AN:

3470

East Asian (EAS)

AF:

0.288

AC:

1488

AN:

5170

South Asian (SAS)

AF:

0.363

AC:

1749

AN:

4820

European-Finnish (FIN)

AF:

0.0892

AC:

947

AN:

10620

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7938

AN:

68018

Other (OTH)

AF:

0.134

AC:

284

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

980

1959

2939

3918

4898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.139

Hom.:

728

Bravo

AF:

0.155

Asia WGS

AF:

0.286

AC:

996

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.7

(source)

DANN

Benign

0.64

PhyloP100

0.056

PromoterAI

0.29

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over