rs201089600

Variant names:

• chr21-41439805-C-A
• rs201089600
• NM_002462.5:c.548C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-41439805-C-A
• chr21-41439805-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002462.5(MX1):​c.548C>A​(p.Thr183Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T183I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MX1 NM_002462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.00

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_002462.5	c.548C>A	p.Thr183Asn	missense_variant	Exon 8 of 17	ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.548C>A	p.Thr183Asn	missense_variant	Exon 8 of 17	1	NM_002462.5	ENSP00000381599.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.83	D;D;D;.;D;D;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	.;T;.;T;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.4	M;M;M;.;.;.;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;.
REVEL	Pathogenic	0.75
Sift	Benign	0.039	D;D;D;D;D;D;.
Sift4G	Uncertain	0.055	T;T;T;D;D;T;D
Polyphen		0.63	P;P;P;.;.;.;.
Vest4		0.68
MutPred		0.75		Loss of glycosylation at T183 (P = 0.1026);Loss of glycosylation at T183 (P = 0.1026);Loss of glycosylation at T183 (P = 0.1026);Loss of glycosylation at T183 (P = 0.1026);Loss of glycosylation at T183 (P = 0.1026);.;Loss of glycosylation at T183 (P = 0.1026);
MVP		0.98
MPC		0.27
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.62
gMVP		0.87

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

Other links and lift over

dbSNP: rs201089600; hg19: chr21-42811732;