NM_002462.5:c.448A>G

Variant names:

• chr21-41439705-A-G
• NM_002462.5:c.448A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002462.5(MX1):​c.448A>G​(p.Ile150Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MX1 NM_002462.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3106702).

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.448A>G	p.Ile150Val	missense	Exon 8 of 17	NP_002453.2	P20591-1
	MX1	NM_001144925.2		c.448A>G	p.Ile150Val	missense	Exon 10 of 19	NP_001138397.1	P20591-1
	MX1	NM_001178046.3		c.448A>G	p.Ile150Val	missense	Exon 6 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.448A>G	p.Ile150Val	missense	Exon 8 of 17	ENSP00000381599.3	P20591-1
	MX1	ENST00000455164.6	TSL:1	c.448A>G	p.Ile150Val	missense	Exon 6 of 15	ENSP00000410523.2	P20591-1
	MX1	ENST00000896042.1		c.448A>G	p.Ile150Val	missense	Exon 8 of 18	ENSP00000566101.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	5.2
DANN	Benign	0.73
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.076	D
MutationAssessor	Benign	0.68	N
PhyloP100		1.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.24
Sift	Benign	0.43	T
Sift4G	Benign	0.37	T
Polyphen		0.15	B
Vest4		0.18
MutPred		0.56		Gain of ubiquitination at K145 (P = 0.1446)
MVP		0.84
MPC		0.11
ClinPred		0.38	T
GERP RS		3.4
Varity_R		0.062
gMVP		0.63
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr21-42811632;