chr1-36066715-T-C

Variant names:

• chr1-36066715-T-C
• rs491603
• NM_024852.4:c.*10970T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024852.4(AGO3):​c.*10970T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,056 control chromosomes in the GnomAD database, including 36,920 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 0.67 (36919 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: AGO3 NM_024852.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693
• Publications: 11 publications found

Genes affected

AGO3 (HGNC:18421): (argonaute RISC catalytic component 3) This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, contains a PAZ domain and a PIWI domain, and may play a role in short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a tandem cluster of closely related family members including argonaute 4 and eukaryotic translation initiation factor 2C, 1. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024852.4. 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
	AGO3	NM_024852.4	MANE Select	c.*10970T>C		3_prime_UTR	Exon 19 of 19	NP_079128.2
	AGO3	NM_177422.3		c.*10970T>C		3_prime_UTR	Exon 17 of 17	NP_803171.1	Q9H9G7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO3	ENST00000373191.9	TSL:2 MANE Select	c.*10970T>C		3_prime_UTR	Exon 19 of 19	ENSP00000362287.3	Q9H9G7-1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102063 AN: 151936 Hom.: 36918 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.695

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

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) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.671 AC: 102092 AN: 152054 Hom.: 36919 Cov.: 32 AF XY: 0.663 AC XY: 49270 AN XY: 74330

African (AFR) AF: 0.451 AC: 18674 AN: 41448

American (AMR) AF: 0.616 AC: 9402 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2708 AN: 3472

East Asian (EAS) AF: 0.238 AC: 1232 AN: 5174

South Asian (SAS) AF: 0.639 AC: 3081 AN: 4822

European-Finnish (FIN) AF: 0.745 AC: 7888 AN: 10582

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56658 AN: 67978

Other (OTH) AF: 0.695 AC: 1465 AN: 2108

Alfa AF: 0.775 Hom.: 84458

Bravo AF: 0.649

Asia WGS AF: 0.484 AC: 1686 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.63
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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: rs491603; hg19: chr1-36532316;