chr2-130345846-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_033416.3(IMP4):c.507G>A(p.Met169Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,614,046 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 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
IMP4
NM_033416.3 missense
NM_033416.3 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 8.99
Genes affected
IMP4 (HGNC:30856): (IMP U3 small nucleolar ribonucleoprotein 4) The protein encoded by this gene, along with IMP3 and MPP10, is part of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP) complex. This complex is necessary for the early cleavage steps of pre-18S ribosomal RNA processing. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]
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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=0.400378).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IMP4 | NM_033416.3 | c.507G>A | p.Met169Ile | missense_variant | 6/9 | ENST00000259239.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IMP4 | ENST00000259239.8 | c.507G>A | p.Met169Ile | missense_variant | 6/9 | 1 | NM_033416.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000139 AC: 35AN: 251078Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135712
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GnomAD4 exome AF: 0.000109 AC: 159AN: 1461848Hom.: 0 Cov.: 33 AF XY: 0.000100 AC XY: 73AN XY: 727230
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74346
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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 | Jun 11, 2021 | The c.507G>A (p.M169I) alteration is located in exon 6 (coding exon 6) of the IMP4 gene. This alteration results from a G to A substitution at nucleotide position 507, causing the methionine (M) at amino acid position 169 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;T;D
Sift4G
Uncertain
D;D;D;D
Polyphen
B;.;.;.
Vest4
MutPred
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;
MVP
MPC
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