rs457274

Variant names:

• chr21-41420558-C-A
• rs457274
• NM_001144925.2:c.-982C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-41420558-C-A
• chr21-41420558-C-G

Variant summary

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

The NM_001144925.2(MX1):​c.-982C>A variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MX1 NM_001144925.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 10 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=-1.01).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MX1	NM_001144925.2	c.-982C>A		5_prime_UTR_variant	Exon 1 of 19		NP_001138397.1
MX1	XM_011529568.3	c.-879C>A		5_prime_UTR_variant	Exon 1 of 20		XP_011527870.1
MX1	XM_017028349.3	c.-1001C>A		5_prime_UTR_variant	Exon 1 of 19		XP_016883838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398600.6	c.-982C>A		5_prime_UTR_variant	Exon 1 of 19	2		ENSP00000381601.2
MX1	ENST00000679445.1	c.-586+118C>A		intron_variant	Intron 1 of 18			ENSP00000505630.1
MX1	ENST00000679464.1	c.-624+118C>A		intron_variant	Intron 1 of 17			ENSP00000505874.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 76 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 50

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.3
DANN	Benign	0.25
PhyloP100		0.051
PromoterAI		-0.00070	Neutral

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

Other links and lift over

dbSNP: rs457274; hg19: chr21-42792485;