Variant 21-41446003-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 (HGNC:):

MX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MX1	NM_002462.5 linkuse as main transcript	c.1135G>A	p.Val379Ile	missense_variant	13/17	ENST00000398598.8	NP_002453.2	P20591-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8 linkuse as main transcript	c.1135G>A	p.Val379Ile	missense_variant	13/17	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

GnomAD3 exomes

AF:

0.514

AC:

128953

AN:

250946

Hom.:

34633

AF XY:

0.523

AC XY:

70950

AN XY:

135620

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 SAS exome

AF:

0.532

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

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.530

Gnomad4 FIN exome

AF:

0.533

Gnomad4 NFE exome

AF:

0.605

Gnomad4 OTH exome

AF:

0.544

GnomAD4 genome

AF:

0.526

AC:

79962

AN:

152030

Hom.:

21625

Cov.:

AF XY:

0.520

AC XY:

38650

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.450

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.529

Gnomad4 FIN

AF:

0.518

Gnomad4 NFE

AF:

0.602

Gnomad4 OTH

AF:

0.535

Alfa

AF:

0.569

Hom.:

65510

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over