11-32602345-G-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006360.6(EIF3M):āc.1071G>Cā(p.Trp357Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 32)
Exomes š: 0.000030 ( 0 hom. )
Consequence
EIF3M
NM_006360.6 missense
NM_006360.6 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 8.90
Genes affected
EIF3M (HGNC:24460): (eukaryotic translation initiation factor 3 subunit M) This gene encodes a protein that is part of the eurkaryotic translation initiation factor 3 complete (eIF-3) required for protein synthesis. Elevated levels of the encoded protein are present in cancer cell lines. Inactivation of the encoded protein has been shown to interfere with translation of herpes virus mRNAs by preventing the association of mRNAs with the ribosomes. A pseudogene of this gene is located on the X chromosome. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.952
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EIF3M | NM_006360.6 | c.1071G>C | p.Trp357Cys | missense_variant | 11/11 | ENST00000531120.6 | NP_006351.2 | |
EIF3M | NM_001307929.2 | c.675G>C | p.Trp225Cys | missense_variant | 8/8 | NP_001294858.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EIF3M | ENST00000531120.6 | c.1071G>C | p.Trp357Cys | missense_variant | 11/11 | 1 | NM_006360.6 | ENSP00000436049.1 | ||
EIF3M | ENST00000524896.5 | c.675G>C | p.Trp225Cys | missense_variant | 8/8 | 2 | ENSP00000436787.1 | |||
EIF3M | ENST00000526267.1 | c.630G>C | p.Trp210Cys | missense_variant | 8/8 | 2 | ENSP00000432139.1 | |||
EIF3M | ENST00000525054.1 | n.*43G>C | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000593 AC: 9AN: 151816Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251172Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135778
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1460344Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 726522
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GnomAD4 genome AF: 0.0000593 AC: 9AN: 151816Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74102
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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 28, 2022 | The c.1071G>C (p.W357C) alteration is located in exon 11 (coding exon 11) of the EIF3M gene. This alteration results from a G to C substitution at nucleotide position 1071, causing the tryptophan (W) at amino acid position 357 to be replaced by a cysteine (C). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0034);.;.;
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