1-35945708-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024852.4(AGO3):​c.36G>C​(p.Gln12His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AGO3
NM_024852.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29558122).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGO3NM_024852.4 linkc.36G>C p.Gln12His missense_variant 2/19 ENST00000373191.9 NP_079128.2 Q9H9G7-1B4E1P5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGO3ENST00000373191.9 linkc.36G>C p.Gln12His missense_variant 2/192 NM_024852.4 ENSP00000362287.3 Q9H9G7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 17, 2022The c.36G>C (p.Q12H) alteration is located in exon 2 (coding exon 2) of the AGO3 gene. This alteration results from a G to C substitution at nucleotide position 36, causing the glutamine (Q) at amino acid position 12 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
.;T;.
Eigen
Uncertain
0.57
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
.;D;D
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.30
T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.5
.;M;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Benign
0.19
Sift
Uncertain
0.011
D;T;D
Sift4G
Benign
0.079
T;T;T
Polyphen
0.84
P;P;P
Vest4
0.48
MutPred
0.38
Loss of catalytic residue at Q12 (P = 0.0489);Loss of catalytic residue at Q12 (P = 0.0489);Loss of catalytic residue at Q12 (P = 0.0489);
MVP
0.26
MPC
0.56
ClinPred
0.96
D
GERP RS
6.2
Varity_R
0.25
gMVP
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-36411309; API