21-41437279-A-G

Variant names:

• chr21-41437279-A-G
• rs468646
• NM_002462.5:c.436+127A>G

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.436+127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000244 in 819,622 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• Publications: 5 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=-0.81).

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.436+127A>G		intron	N/A	NP_002453.2	P20591-1
	MX1	NM_001144925.2		c.436+127A>G		intron	N/A	NP_001138397.1	P20591-1
	MX1	NM_001178046.3		c.436+127A>G		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.436+127A>G		intron	N/A	ENSP00000381599.3	P20591-1
	MX1	ENST00000455164.6	TSL:1	c.436+127A>G		intron	N/A	ENSP00000410523.2	P20591-1
	MX1	ENST00000896042.1		c.436+127A>G		intron	N/A	ENSP00000566101.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000244 AC: 2 AN: 819622 Hom.: 0 AF XY: 0.00000477 AC XY: 2 AN XY: 419118

African (AFR) AF: 0.00 AC: 0 AN: 20188

American (AMR) AF: 0.00 AC: 0 AN: 28704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16328

East Asian (EAS) AF: 0.00 AC: 0 AN: 36470

South Asian (SAS) AF: 0.0000181 AC: 1 AN: 55390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4258

European-Non Finnish (NFE) AF: 0.00000173 AC: 1 AN: 576762

Other (OTH) AF: 0.00 AC: 0 AN: 38158

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 9618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.82
PhyloP100		0.78

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: rs468646; hg19: chr21-42809206;