7-151119991-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_031946.7(AGAP3):c.974C>T(p.Thr325Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,613,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
AGAP3
NM_031946.7 missense
NM_031946.7 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 3.53
Genes affected
AGAP3 (HGNC:16923): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 3) This gene encodes an essential component of the N-methyl-D-aspartate (NMDA) receptor signaling complex which mediates long-term potentiation in synapses by linking activation of NMDA receptor to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking. The encoded protein contains an N-terminal GTPase-like domain, a pleckstrin homology domain, an ArfGAP domain and several C-terminal ankryn repeat domains. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.076630175).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGAP3 | NM_031946.7 | c.974C>T | p.Thr325Met | missense_variant | 8/18 | ENST00000397238.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGAP3 | ENST00000397238.7 | c.974C>T | p.Thr325Met | missense_variant | 8/18 | 1 | NM_031946.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000183 AC: 45AN: 245658Hom.: 0 AF XY: 0.000127 AC XY: 17AN XY: 133886
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GnomAD4 exome AF: 0.000175 AC: 256AN: 1461186Hom.: 0 Cov.: 32 AF XY: 0.000179 AC XY: 130AN XY: 726958
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74492
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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 submitter | clinical testing | Ambry Genetics | May 05, 2023 | The c.974C>T (p.T325M) alteration is located in exon 8 (coding exon 8) of the AGAP3 gene. This alteration results from a C to T substitution at nucleotide position 974, causing the threonine (T) at amino acid position 325 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;N;D
REVEL
Benign
Sift
Benign
D;D;D;.;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
0.82, 1.0
.;.;P;.;D;.
Vest4
MVP
MPC
1.2
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at