21-41452734-A-C

Variant names:

• chr21-41452734-A-C
• NM_002462.5:c.1623A>C
• MX1 p.Ala541Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002462.5(MX1):​c.1623A>C​(p.Ala541Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A541A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MX1 NM_002462.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.40
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-5.4 with no splicing effect.

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.1623A>C	p.Ala541Ala	synonymous	Exon 16 of 17	NP_002453.2	P20591-1
	MX1	NM_001144925.2		c.1623A>C	p.Ala541Ala	synonymous	Exon 18 of 19	NP_001138397.1	P20591-1
	MX1	NM_001178046.3		c.1623A>C	p.Ala541Ala	synonymous	Exon 14 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.1623A>C	p.Ala541Ala	synonymous	Exon 16 of 17	ENSP00000381599.3	P20591-1
	MX1	ENST00000455164.6	TSL:1	c.1623A>C	p.Ala541Ala	synonymous	Exon 14 of 15	ENSP00000410523.2	P20591-1
	MX1	ENST00000491110.1	TSL:1	n.430A>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.026
DANN	Benign	0.28
PhyloP100		-5.4

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-42824661;