chr2-227536954-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004504.5(AGFG1):c.1339T>C(p.Ser447Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,026 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
AGFG1
NM_004504.5 missense
NM_004504.5 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 2.92
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16987374).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGFG1 | NM_004504.5 | c.1339T>C | p.Ser447Pro | missense_variant | 10/13 | ENST00000310078.13 | |
AGFG1 | NM_001135187.2 | c.1411T>C | p.Ser471Pro | missense_variant | 11/14 | ||
AGFG1 | NM_001135188.2 | c.1339T>C | p.Ser447Pro | missense_variant | 10/13 | ||
AGFG1 | NM_001135189.2 | c.1219T>C | p.Ser407Pro | missense_variant | 9/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGFG1 | ENST00000310078.13 | c.1339T>C | p.Ser447Pro | missense_variant | 10/13 | 1 | NM_004504.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251272Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135812
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460846Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726692
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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 | Aug 22, 2023 | The c.1411T>C (p.S471P) alteration is located in exon 11 (coding exon 11) of the AGFG1 gene. This alteration results from a T to C substitution at nucleotide position 1411, causing the serine (S) at amino acid position 471 to be replaced by a proline (P). 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
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.0070, 0.0010, 0.0040
.;B;.;B;B
Vest4
MutPred
0.24
.;Gain of relative solvent accessibility (P = 0.0023);.;.;Gain of relative solvent accessibility (P = 0.0023);
MVP
MPC
ClinPred
T
GERP RS
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