rs716924

Variant names:

• chr1-35958737-T-C
• rs716924
• NM_024852.4:c.192-8218T>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.192-8218T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,116 control chromosomes in the GnomAD database, including 3,784 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 0.15 (3784 hom., cov: 32)
• Consequence: AGO3 NM_024852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.663 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.192-8218T>C		intron	N/A	NP_079128.2
	AGO3	NM_177422.3		c.-254+12874T>C		intron	N/A	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.192-8218T>C		intron	N/A	ENSP00000362287.3	Q9H9G7-1
	AGO3	ENST00000246314.10	TSL:1	c.-254+12874T>C		intron	N/A	ENSP00000246314.6	Q9H9G7-2
	AGO3	ENST00000870913.1		c.192-8218T>C		intron	N/A	ENSP00000540972.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22101 AN: 152000 Hom.: 3760 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00842

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22175 AN: 152116 Hom.: 3784 Cov.: 32 AF XY: 0.152 AC XY: 11318 AN XY: 74376

African (AFR) AF: 0.302 AC: 12504 AN: 41450

American (AMR) AF: 0.265 AC: 4042 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3470

East Asian (EAS) AF: 0.681 AC: 3527 AN: 5176

South Asian (SAS) AF: 0.0692 AC: 334 AN: 4828

European-Finnish (FIN) AF: 0.0749 AC: 793 AN: 10586

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00841 AC: 572 AN: 68020

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.0776 Hom.: 698

Bravo AF: 0.175

Asia WGS AF: 0.314 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.5
DANN	Benign	0.66
PhyloP100		2.0
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: rs716924; hg19: chr1-36424338;