rs467960

Variant names:

• chr21-41440964-C-T
• rs467960
• NM_002462.5:c.669C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002462.5(MX1):​c.669C>T​(p.Ile223Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,613,894 control chromosomes in the GnomAD database, including 245,356 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 0.48 (18738 hom., cov: 32)
  • Exomes 𝑓: 0.55 (226618 hom.)
• Consequence: MX1 NM_002462.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 21 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]

MX1-AS1 (HGNC:40383):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=-2.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 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.669C>T	p.Ile223Ile	synonymous	Exon 9 of 17	NP_002453.2	P20591-1
	MX1	NM_001144925.2		c.669C>T	p.Ile223Ile	synonymous	Exon 11 of 19	NP_001138397.1	P20591-1
	MX1	NM_001178046.3		c.669C>T	p.Ile223Ile	synonymous	Exon 7 of 15	NP_001171517.1	P20591-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	ENST00000398598.8	TSL:1 MANE Select	c.669C>T	p.Ile223Ile	synonymous	Exon 9 of 17	ENSP00000381599.3	P20591-1
	MX1	ENST00000455164.6	TSL:1	c.669C>T	p.Ile223Ile	synonymous	Exon 7 of 15	ENSP00000410523.2	P20591-1
	MX1	ENST00000896042.1		c.669C>T	p.Ile223Ile	synonymous	Exon 9 of 18	ENSP00000566101.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72842 AN: 151988 Hom.: 18725 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.498

GnomAD2 exomes AF: 0.466 AC: 117190 AN: 251410 AF XY: 0.472

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.448

Gnomad EAS exome AF: 0.105

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.482

GnomAD4 exome AF: 0.546 AC: 798279 AN: 1461788 Hom.: 226618 Cov.: 53 AF XY: 0.542 AC XY: 393895 AN XY: 727190

African (AFR) AF: 0.344 AC: 11503 AN: 33478

American (AMR) AF: 0.391 AC: 17495 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 11612 AN: 26132

East Asian (EAS) AF: 0.0897 AC: 3561 AN: 39698

South Asian (SAS) AF: 0.373 AC: 32156 AN: 86258

European-Finnish (FIN) AF: 0.516 AC: 27545 AN: 53406

Middle Eastern (MID) AF: 0.462 AC: 2664 AN: 5764

European-Non Finnish (NFE) AF: 0.595 AC: 661198 AN: 1111938

Other (OTH) AF: 0.506 AC: 30545 AN: 60394

GnomAD4 genome AF: 0.479 AC: 72905 AN: 152106 Hom.: 18738 Cov.: 32 AF XY: 0.471 AC XY: 34994 AN XY: 74338

African (AFR) AF: 0.351 AC: 14566 AN: 41502

American (AMR) AF: 0.472 AC: 7225 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3472

East Asian (EAS) AF: 0.102 AC: 528 AN: 5164

South Asian (SAS) AF: 0.367 AC: 1767 AN: 4816

European-Finnish (FIN) AF: 0.503 AC: 5321 AN: 10586

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40105 AN: 67954

Other (OTH) AF: 0.497 AC: 1050 AN: 2114

Alfa AF: 0.538 Hom.: 19955

Bravo AF: 0.469

Asia WGS AF: 0.248 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	6.5
DANN	Benign	0.83
PhyloP100		-2.0
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: rs467960; hg19: chr21-42812891; COSMIC: COSV55818088; COSMIC: COSV55818088;