Variant chr21-41441800-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002462.5(MX1):c.815A>G(p.Lys272Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MX1
NM_002462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MX1	NM_002462.5 linkuse as main transcript	c.815A>G	p.Lys272Arg	missense_variant	10/17	ENST00000398598.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MX1	ENST00000398598.8 linkuse as main transcript	c.815A>G	p.Lys272Arg	missense_variant	10/17	1	NM_002462.5	P1	P20591-1
	ENST00000411427.3 linkuse as main transcript	n.372T>C		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2024

The c.815A>G (p.K272R) alteration is located in exon 12 (coding exon 6) of the MX1 gene. This alteration results from a A to G substitution at nucleotide position 815, causing the lysine (K) at amino acid position 272 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.0097

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T;T;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.93

.;D;.;D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.44

T;T;T;T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.3

M;M;M;.;M

MutationTaster

Benign

0.98

D;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

N;N;N;N;.

REVEL

Uncertain

0.44

Sift

Benign

0.33

T;T;T;T;.

Sift4G

Benign

0.39

T;T;T;T;T

Polyphen

1.0

D;D;D;.;.

Vest4

0.26

MutPred

0.66

Gain of MoRF binding (P = 0.0669);Gain of MoRF binding (P = 0.0669);Gain of MoRF binding (P = 0.0669);.;Gain of MoRF binding (P = 0.0669);

MVP

0.88

MPC

0.27

ClinPred

0.93

GERP RS

5.1

Varity_R

0.35

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over