Variant 11-32602290-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006360.6(EIF3M):c.1016A>G(p.His339Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,438 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

EIF3M
NM_006360.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.29

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]

EIF3M links:

EIF3M (HGNC:):

EIF3M links:

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
EIF3M	NM_006360.6 linkuse as main transcript	c.1016A>G	p.His339Arg	missense_variant	11/11	ENST00000531120.6	NP_006351.2	Q7L2H7-1
EIF3M	NM_001307929.2 linkuse as main transcript	c.620A>G	p.His207Arg	missense_variant	8/8		NP_001294858.1	Q7L2H7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EIF3M	ENST00000531120.6 linkuse as main transcript	c.1016A>G	p.His339Arg	missense_variant	11/11	1	NM_006360.6	ENSP00000436049.1	Q7L2H7-1
EIF3M	ENST00000524896.5 linkuse as main transcript	c.620A>G	p.His207Arg	missense_variant	8/8	2		ENSP00000436787.1	Q7L2H7-2
EIF3M	ENST00000526267.1 linkuse as main transcript	c.575A>G	p.His192Arg	missense_variant	8/8	2		ENSP00000432139.1	H0YCQ8
EIF3M	ENST00000525054.1 linkuse as main transcript	n.580A>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250878

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459438

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

725984

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Mar 18, 2024

The c.1016A>G (p.H339R) alteration is located in exon 11 (coding exon 11) of the EIF3M gene. This alteration results from a A to G substitution at nucleotide position 1016, causing the histidine (H) at amino acid position 339 to be replaced by an arginine (R). 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

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;.;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

M;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

0.77

P;.;.

Vest4

0.80

MutPred

0.62

Gain of MoRF binding (P = 0.025);.;.;

MVP

0.70

MPC

1.3

ClinPred

0.86

GERP RS

5.8

Varity_R

0.70

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over