11-32588710-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006360.6(EIF3M):​c.292C>T​(p.Arg98Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 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 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

EIF3M
NM_006360.6 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99
Variant links:
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]

Genome browser will be placed here

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 Protein UniProt
EIF3MNM_006360.6 linkuse as main transcriptc.292C>T p.Arg98Cys missense_variant 3/11 ENST00000531120.6 NP_006351.2 Q7L2H7-1
EIF3MNM_001307929.2 linkuse as main transcriptc.43-837C>T intron_variant NP_001294858.1 Q7L2H7-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EIF3MENST00000531120.6 linkuse as main transcriptc.292C>T p.Arg98Cys missense_variant 3/111 NM_006360.6 ENSP00000436049.1 Q7L2H7-1

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000596
AC:
15
AN:
251484
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000540
AC:
79
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.0000509
AC XY:
37
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000638
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsMay 24, 2023The c.292C>T (p.R98C) alteration is located in exon 3 (coding exon 3) of the EIF3M gene. This alteration results from a C to T substitution at nucleotide position 292, causing the arginine (R) at amino acid position 98 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.077
T;.;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.11
Sift
Benign
0.19
T;D;D
Sift4G
Uncertain
0.029
D;D;D
Polyphen
0.99
D;.;.
Vest4
0.67
MutPred
0.42
Loss of disorder (P = 0.0059);.;.;
MVP
0.22
MPC
0.12
ClinPred
0.22
T
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.37
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.37
Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775868574; hg19: chr11-32610256; COSMIC: COSV60072330; COSMIC: COSV60072330; API