21-41421864-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144925.2(MX1):c.-696C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,274 control chromosomes in the GnomAD database, including 15,341 homozygotes. 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 0.45 (15290 hom., cov: 32)
  • Exomes 𝑓: 0.38 (51 hom.)
• Consequence: MX1 NM_001144925.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MX1	NM_001144925.2	c.-696C>G		5_prime_UTR_variant	2/19
MX1	XM_011529568.3	c.-593C>G		5_prime_UTR_variant	2/20
MX1	XM_017028349.3	c.-715C>G		5_prime_UTR_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MX1	ENST00000398600.6	c.-696C>G		5_prime_UTR_variant	2/19	2		P1
MX1	ENST00000413778.6	c.-612C>G		5_prime_UTR_variant	2/20	5		P1
MX1	ENST00000679464.1	c.-597C>G		5_prime_UTR_variant	2/18			P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67883 AN: 151498 Hom.: 15289 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.383 AC: 251 AN: 656 Hom.: 51 Cov.: 0 AF XY: 0.388 AC XY: 202 AN XY: 520

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.688

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.448 AC: 67920 AN: 151618 Hom.: 15290 Cov.: 32 AF XY: 0.449 AC XY: 33259 AN XY: 74064

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.456

Alfa AF: 0.420 Hom.: 1646

Bravo AF: 0.457

Asia WGS AF: 0.492 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.60

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: rs459482; hg19: chr21-42793791;