Genetic Variant AGO3:c.*13298G>T (chr1-36069043-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024852.4(AGO3):c.*13298G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,168 control chromosomes in the GnomAD database, including 43,481 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 0.72 ( 43476 hom., cov: 32)

Exomes 𝑓: 0.81 ( 5 hom. )

Consequence

AGO3
NM_024852.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.762

Publications

8 publications found

Variant links:

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]

AGO3 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 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.*13298G>T		3_prime_UTR	Exon 19 of 19	NP_079128.2
	AGO3	NM_177422.3		c.*13298G>T		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.*13298G>T		3_prime_UTR	Exon 19 of 19	ENSP00000362287.3	Q9H9G7-1

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109943

AN:

152034

Hom.:

43484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.961

Gnomad AMR

AF:

0.665

Gnomad ASJ

AF:

0.864

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.841

Gnomad FIN

AF:

0.821

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.755

GnomAD4 exome

AF:

0.813

AC:

AN:

Hom.:

Cov.:

AF XY:

0.800

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.917

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.723

AC:

109958

AN:

152152

Hom.:

43476

Cov.:

AF XY:

0.717

AC XY:

53361

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.428

AC:

17765

AN:

41476

American (AMR)

AF:

0.664

AC:

10151

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.864

AC:

2999

AN:

3470

East Asian (EAS)

AF:

0.319

AC:

1649

AN:

5176

South Asian (SAS)

AF:

0.840

AC:

4053

AN:

4824

European-Finnish (FIN)

AF:

0.821

AC:

8700

AN:

10598

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.910

AC:

61915

AN:

68014

Other (OTH)

AF:

0.755

AC:

1589

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1191

2382

3574

4765

5956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.834

Hom.:

42148

Bravo

AF:

0.691

Asia WGS

AF:

0.619

AC:

2153

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.5

(source)

DANN

Benign

0.66

PhyloP100

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over