chr2-227554478-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004504.5(AGFG1):c.1672A>G(p.Thr558Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,548 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
AGFG1
NM_004504.5 missense
NM_004504.5 missense
Scores
4
9
4
Clinical Significance
Conservation
PhyloP100: 8.31
Genes affected
AGFG1 (HGNC:5175): (ArfGAP with FG repeats 1) The protein encoded by this gene is related to nucleoporins, a class of proteins that mediate nucleocytoplasmic transport. The encoded protein binds the activation domain of the human immunodeficiency virus Rev protein when Rev is assembled onto its RNA target, and is required for the nuclear export of Rev-directed RNAs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGFG1 | NM_004504.5 | c.1672A>G | p.Thr558Ala | missense_variant | 13/13 | ENST00000310078.13 | |
AGFG1 | NM_001135187.2 | c.1738A>G | p.Thr580Ala | missense_variant | 14/14 | ||
AGFG1 | NM_001135188.2 | c.1666A>G | p.Thr556Ala | missense_variant | 13/13 | ||
AGFG1 | NM_001135189.2 | c.1552A>G | p.Thr518Ala | missense_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGFG1 | ENST00000310078.13 | c.1672A>G | p.Thr558Ala | missense_variant | 13/13 | 1 | NM_004504.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152182Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251108Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135728
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461366Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726992
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74340
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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 | Dec 14, 2023 | The c.1738A>G (p.T580A) alteration is located in exon 14 (coding exon 14) of the AGFG1 gene. This alteration results from a A to G substitution at nucleotide position 1738, causing the threonine (T) at amino acid position 580 to be replaced by an alanine (A). 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
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;T;D;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
1.0, 1.0, 0.99
.;D;.;D;D
Vest4
MutPred
0.11
.;Loss of glycosylation at T558 (P = 0.018);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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