NM_002462.5:c.-98+397C>T

Variant names:

• chr21-41428263-C-T
• rs461093
• NM_002462.5:c.-98+397C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002462.5(MX1):​c.-98+397C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 152,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000059 (0 hom., cov: 33)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.-98+397C>T		intron	N/A	NP_002453.2	P20591-1
	MX1	NM_001144925.2		c.-98+397C>T		intron	N/A	NP_001138397.1	P20591-1
	MX1	NM_001178046.3		c.-22+397C>T		intron	N/A	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.-98+397C>T		intron	N/A	ENSP00000381599.3	P20591-1
	MX1	ENST00000455164.6	TSL:1	c.-22+397C>T		intron	N/A	ENSP00000410523.2	P20591-1
	MX1	ENST00000896042.1		c.-98+397C>T		intron	N/A	ENSP00000566101.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152120 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74296

African (AFR) AF: 0.0000483 AC: 2 AN: 41432

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.45
PhyloP100		0.21

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: rs461093; hg19: chr21-42800190;