rs464138

Positions:

• chr21-41426246-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002462.5(MX1):​c.-326A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 153,632 control chromosomes in the GnomAD database, including 11,183 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 0.36 (11030 hom., cov: 33)
  • Exomes 𝑓: 0.46 (153 hom.)
• Consequence: MX1 NM_002462.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.34

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MX1	NM_002462.5	c.-326A>C		5_prime_UTR_variant	1/17	ENST00000398598.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MX1	ENST00000398598.8	c.-326A>C		5_prime_UTR_variant	1/17	1	NM_002462.5	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55227 AN: 152022 Hom.: 11036 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.457 AC: 682 AN: 1492 Hom.: 153 Cov.: 0 AF XY: 0.452 AC XY: 392 AN XY: 868

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.363 AC: 55230 AN: 152140 Hom.: 11030 Cov.: 33 AF XY: 0.368 AC XY: 27381 AN XY: 74382

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.392

Alfa AF: 0.384 Hom.: 3374

Bravo AF: 0.360

Asia WGS AF: 0.460 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.29

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: rs464138; hg19: chr21-42798173;