rs1050008

Variant names:

• chr21-41452734-A-G
• rs1050008
• NM_002462.5:c.1623A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-41452734-A-G
• chr21-41452734-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (3166 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22642 hom.)
• Consequence: MX1 NM_002462.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.40
• Publications: 23 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	NM_002462.5	MANE Select	c.1623A>G	p.Ala541Ala	synonymous	Exon 16 of 17	NP_002453.2
	MX1	NM_001144925.2		c.1623A>G	p.Ala541Ala	synonymous	Exon 18 of 19	NP_001138397.1
	MX1	NM_001178046.3		c.1623A>G	p.Ala541Ala	synonymous	Exon 14 of 15	NP_001171517.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	ENST00000398598.8	TSL:1 MANE Select	c.1623A>G	p.Ala541Ala	synonymous	Exon 16 of 17	ENSP00000381599.3
	MX1	ENST00000455164.6	TSL:1	c.1623A>G	p.Ala541Ala	synonymous	Exon 14 of 15	ENSP00000410523.2
	MX1	ENST00000491110.1	TSL:1	n.430A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28563 AN: 152004 Hom.: 3156 Cov.: 32

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

GnomAD2 exomes AF: 0.206 AC: 51753 AN: 251430 AF XY: 0.205

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 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.: 32 AF XY: 0.163 AC XY: 118520 AN XY: 727222

African (AFR) AF: 0.240 AC: 8026 AN: 33476

American (AMR) AF: 0.232 AC: 10371 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 2379 AN: 26136

East Asian (EAS) AF: 0.455 AC: 18082 AN: 39700

South Asian (SAS) AF: 0.289 AC: 24890 AN: 86256

European-Finnish (FIN) AF: 0.210 AC: 11204 AN: 53418

Middle Eastern (MID) AF: 0.162 AC: 936 AN: 5768

European-Non Finnish (NFE) AF: 0.132 AC: 147116 AN: 1111970

Other (OTH) AF: 0.173 AC: 10466 AN: 60394

GnomAD4 genome AF: 0.188 AC: 28608 AN: 152122 Hom.: 3166 Cov.: 32 AF XY: 0.196 AC XY: 14551 AN XY: 74366

African (AFR) AF: 0.235 AC: 9746 AN: 41500

American (AMR) AF: 0.161 AC: 2459 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 296 AN: 3472

East Asian (EAS) AF: 0.464 AC: 2395 AN: 5164

South Asian (SAS) AF: 0.296 AC: 1425 AN: 4814

European-Finnish (FIN) AF: 0.214 AC: 2264 AN: 10586

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9477 AN: 67992

Other (OTH) AF: 0.168 AC: 355 AN: 2112

Alfa AF: 0.155 Hom.: 7485

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.037
DANN	Benign	0.31
PhyloP100		-5.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1050008; hg19: chr21-42824661; COSMIC: COSV55819498; COSMIC: COSV55819498;