rs469304

Positions:

• chr21-41452806-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002462.5(MX1):​c.1695G>A​(p.Gln565=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MX1	NM_002462.5	c.1695G>A	p.Gln565=	synonymous_variant	16/17	ENST00000398598.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MX1	ENST00000398598.8	c.1695G>A	p.Gln565=	synonymous_variant	16/17	1	NM_002462.5	P1

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

GnomAD3 exomes AF: 0.417 AC: 104959 AN: 251416 Hom.: 25826 AF XY: 0.430 AC XY: 58452 AN XY: 135880

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 SAS exome AF: 0.382

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

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.471

Gnomad4 EAS exome AF: 0.00471

Gnomad4 SAS exome AF: 0.381

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.466

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

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.00793

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.406

Alfa AF: 0.488 Hom.: 13648

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.039
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

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