dbSNP rs1050008: MX1:p.Ala541Ala (chr21-41452734-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.206

AC:

51753

AN:

251430

Hom.:

6607

AF XY:

0.205

AC XY:

27876

AN XY:

135890

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 SAS exome

AF:

0.291

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

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.0910

Gnomad4 EAS exome

AF:

0.455

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.188

AC:

28608

AN:

152122

Hom.:

3166

Cov.:

AF XY:

0.196

AC XY:

14551

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.0853

Gnomad4 EAS

AF:

0.464

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.148

Hom.:

3357

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

DANN

Benign

0.31

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