chr21-41420558-C-G

Position:

• chr21-41420558-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.-982C>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 0.352 in 152,148 control chromosomes in the GnomAD database, including 10,591 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 0.35 (10587 hom., cov: 33)
  • Exomes 𝑓: 0.36 (4 hom.)
• Consequence: MX1 NM_001144925.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MX1	NM_001144925.2	c.-982C>G		5_prime_UTR_variant	1/19		NP_001138397.1
MX1	XM_011529568.3	c.-879C>G		5_prime_UTR_variant	1/20		XP_011527870.1
MX1	XM_017028349.3	c.-1001C>G		5_prime_UTR_variant	1/19		XP_016883838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398600	c.-982C>G		5_prime_UTR_variant	1/19	2		ENSP00000381601.2
MX1	ENST00000679445.1	c.-586+118C>G		intron_variant				ENSP00000505630.1
MX1	ENST00000679464.1	c.-624+118C>G		intron_variant				ENSP00000505874.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53551 AN: 151954 Hom.: 10588 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.355 AC: 27 AN: 76 Hom.: 4 Cov.: 0 AF XY: 0.440 AC XY: 22 AN XY: 50

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.352 AC: 53566 AN: 152072 Hom.: 10587 Cov.: 33 AF XY: 0.357 AC XY: 26548 AN XY: 74314

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.377

Alfa AF: 0.366 Hom.: 1400

Bravo AF: 0.347

Asia WGS AF: 0.471 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	6.8
DANN	Benign	0.61

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: rs457274; hg19: chr21-42792485;