Genetic Variant NM_002462.5:c.436+127A>G (chr21-41437279-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.776

Publications

5 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5 link	c.436+127A>G		intron_variant	Intron 7 of 16	ENST00000398598.8	NP_002453.2	P20591-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8 link	c.436+127A>G		intron_variant	Intron 7 of 16	1	NM_002462.5	ENSP00000381599.3		P20591-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000244

AC:

AN:

819622

Hom.:

AF XY:

0.00000477

AC XY:

AN XY:

419118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20188

American (AMR)

AF:

0.00

AC:

AN:

28704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16328

East Asian (EAS)

AF:

0.00

AC:

AN:

36470

South Asian (SAS)

AF:

0.0000181

AC:

AN:

55390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4258

European-Non Finnish (NFE)

AF:

0.00000173

AC:

AN:

576762

Other (OTH)

AF:

0.00

AC:

AN:

38158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

9618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.0

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over