7-23469977-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006547.3(IGF2BP3):c.134C>T(p.Pro45Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,176 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: 0.0000014 ( 0 hom. )
Consequence
IGF2BP3
NM_006547.3 missense
NM_006547.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 9.47
Genes affected
IGF2BP3 (HGNC:28868): (insulin like growth factor 2 mRNA binding protein 3) The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5' UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. A pseudogene exists on chromosome 7, and there are putative pseudogenes on other chromosomes. [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=0.42382756).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF2BP3 | NM_006547.3 | c.134C>T | p.Pro45Leu | missense_variant | 1/15 | ENST00000258729.8 | |
IGF2BP3 | XM_011515089.3 | c.134C>T | p.Pro45Leu | missense_variant | 1/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF2BP3 | ENST00000258729.8 | c.134C>T | p.Pro45Leu | missense_variant | 1/15 | 1 | NM_006547.3 | P1 | |
IGF2BP3 | ENST00000468005.1 | n.384C>T | non_coding_transcript_exon_variant | 1/5 | 5 | ||||
IGF2BP3 | ENST00000476938.5 | n.40C>T | non_coding_transcript_exon_variant | 1/5 | 2 | ||||
IGF2BP3 | ENST00000421467.6 | c.134C>T | p.Pro45Leu | missense_variant, NMD_transcript_variant | 1/12 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460064Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726302
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
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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 10, 2021 | The c.134C>T (p.P45L) alteration is located in exon 1 (coding exon 1) of the IGF2BP3 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the proline (P) at amino acid position 45 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Gain of catalytic residue at P45 (P = 0.1405);
MVP
MPC
ClinPred
D
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