21-41426103-C-T

Variant names:

• chr21-41426103-C-T
• rs17000900
• ENST00000455164.6:c.-294C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000455164.6(MX1):​c.-294C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,212 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MX1 ENST00000455164.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 29 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000455164.6. 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_001144925.2		c.-308-1103C>T		intron	N/A	NP_001138397.1	P20591-1
	MX1	NM_002462.5	MANE Select	c.-469C>T		upstream_gene	N/A	NP_002453.2	P20591-1
	MX1	NM_001178046.3		c.-294C>T		upstream_gene	N/A	NP_001171517.1	P20591-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	ENST00000455164.6	TSL:1	c.-294C>T		5_prime_UTR	Exon 1 of 15	ENSP00000410523.2	P20591-1
	MX1	ENST00000915292.1		c.-311C>T		splice_region	Exon 1 of 17	ENSP00000585351.1
	MX1	ENST00000419044.6	TSL:3	c.-367C>T		5_prime_UTR	Exon 1 of 17	ENSP00000392151.2	P20591-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 21622 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 11394

African (AFR) AF: 0.00 AC: 0 AN: 538

American (AMR) AF: 0.00 AC: 0 AN: 440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 604

East Asian (EAS) AF: 0.00 AC: 0 AN: 2320

South Asian (SAS) AF: 0.00 AC: 0 AN: 154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 86

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 13662

Other (OTH) AF: 0.00 AC: 0 AN: 1196

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 381

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		-0.14
PromoterAI		0.42	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

dbSNP: rs17000900;

hg19: chr21-42798030;