Variant chr21-41441771-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002462.5(MX1):c.786C>G(p.Asp262Glu) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

MX1
NM_002462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.55

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32211205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MX1	NM_002462.5 linkuse as main transcript	c.786C>G	p.Asp262Glu	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.786C>G	p.Asp262Glu	missense_variant	10/17	1	NM_002462.5	P1	P20591-1
	ENST00000411427.3 linkuse as main transcript	n.401G>C		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152160

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Sep 22, 2022

The c.786C>G (p.D262E) alteration is located in exon 12 (coding exon 6) of the MX1 gene. This alteration results from a C to G substitution at nucleotide position 786, causing the aspartic acid (D) at amino acid position 262 to be replaced by a glutamic acid (E). 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

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.7

DANN

Benign

0.84

DEOGEN2

Benign

0.33

T;T;T;T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.61

.;T;.;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.32

T;T;T;T;T

MetaSVM

Uncertain

-0.092

MutationAssessor

Uncertain

2.4

M;M;M;.;M

MutationTaster

Benign

0.78

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.8

N;N;N;N;.

REVEL

Uncertain

0.43

Sift

Benign

0.10

T;T;T;T;.

Sift4G

Benign

0.48

T;T;T;T;T

Polyphen

0.98

D;D;D;.;.

Vest4

0.11

MutPred

0.74

Gain of ubiquitination at K259 (P = 0.0822);Gain of ubiquitination at K259 (P = 0.0822);Gain of ubiquitination at K259 (P = 0.0822);.;Gain of ubiquitination at K259 (P = 0.0822);

MVP

0.83

MPC

0.24

ClinPred

0.63

GERP RS

-3.3

Varity_R

0.29

gMVP

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over