rs469304

Variant names:

• chr21-41452806-G-A
• rs469304
• NM_002462.5:c.1695G>A

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.1695G>A​(p.Gln565Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,613,828 control chromosomes in the GnomAD database, including 220,990 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 0.41 (15124 hom., cov: 31)
  • Exomes 𝑓: 0.52 (205866 hom.)
• Consequence: MX1 NM_002462.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 15 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=-0.88).
• BP7: Synonymous conserved (PhyloP=-2.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 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.1695G>A	p.Gln565Gln	synonymous	Exon 16 of 17	NP_002453.2
	MX1	NM_001144925.2		c.1695G>A	p.Gln565Gln	synonymous	Exon 18 of 19	NP_001138397.1
	MX1	NM_001178046.3		c.1695G>A	p.Gln565Gln	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.1695G>A	p.Gln565Gln	synonymous	Exon 16 of 17	ENSP00000381599.3
	MX1	ENST00000455164.6	TSL:1	c.1695G>A	p.Gln565Gln	synonymous	Exon 14 of 15	ENSP00000410523.2
	MX1	ENST00000491110.1	TSL:1	n.502G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62394 AN: 151852 Hom.: 15126 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.00811

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.409

GnomAD2 exomes AF: 0.417 AC: 104959 AN: 251416 AF XY: 0.430

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.251

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.00473

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.435

GnomAD4 exome AF: 0.515 AC: 753231 AN: 1461856 Hom.: 205866 Cov.: 57 AF XY: 0.513 AC XY: 372912 AN XY: 727214

African (AFR) AF: 0.194 AC: 6493 AN: 33480

American (AMR) AF: 0.261 AC: 11655 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 12315 AN: 26136

East Asian (EAS) AF: 0.00471 AC: 187 AN: 39700

South Asian (SAS) AF: 0.381 AC: 32887 AN: 86252

European-Finnish (FIN) AF: 0.494 AC: 26411 AN: 53418

Middle Eastern (MID) AF: 0.394 AC: 2274 AN: 5768

European-Non Finnish (NFE) AF: 0.569 AC: 632893 AN: 1111986

Other (OTH) AF: 0.466 AC: 28116 AN: 60392

GnomAD4 genome AF: 0.411 AC: 62410 AN: 151972 Hom.: 15124 Cov.: 31 AF XY: 0.401 AC XY: 29785 AN XY: 74248

African (AFR) AF: 0.211 AC: 8743 AN: 41450

American (AMR) AF: 0.338 AC: 5155 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3464

East Asian (EAS) AF: 0.00793 AC: 41 AN: 5168

South Asian (SAS) AF: 0.371 AC: 1788 AN: 4820

European-Finnish (FIN) AF: 0.484 AC: 5107 AN: 10550

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38275 AN: 67940

Other (OTH) AF: 0.406 AC: 857 AN: 2110

Alfa AF: 0.485 Hom.: 14994

Bravo AF: 0.388

Asia WGS AF: 0.174 AC: 608 AN: 3478

EpiCase AF: 0.543

EpiControl AF: 0.534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.039
DANN	Benign	0.35
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs469304; hg19: chr21-42824733; COSMIC: COSV55819307; COSMIC: COSV55819307;