Genetic Variant EIF3M:p.His339Leu (chr11-32602290-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006360.6(EIF3M):c.1016A>T(p.His339Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,438 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H339R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EIF3M
NM_006360.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.29

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3M	NM_006360.6 link	c.1016A>T	p.His339Leu	missense_variant	Exon 11 of 11	ENST00000531120.6	NP_006351.2	Q7L2H7-1
EIF3M	NM_001307929.2 link	c.620A>T	p.His207Leu	missense_variant	Exon 8 of 8		NP_001294858.1	Q7L2H7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EIF3M	ENST00000531120.6 link	c.1016A>T	p.His339Leu	missense_variant	Exon 11 of 11	1	NM_006360.6	ENSP00000436049.1	Q7L2H7-1
EIF3M	ENST00000524896.5 link	c.620A>T	p.His207Leu	missense_variant	Exon 8 of 8	2		ENSP00000436787.1	Q7L2H7-2
EIF3M	ENST00000526267.1 link	c.575A>T	p.His192Leu	missense_variant	Exon 8 of 8	2		ENSP00000432139.1	H0YCQ8
EIF3M	ENST00000525054.1 link	n.580A>T		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459438

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110624

Other (OTH)

AF:

0.00

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.32

T;.;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.73

D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

M;.;.

PhyloP100

8.3

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.1

D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.19

B;.;.

Vest4

0.80

MutPred

0.67

Loss of disorder (P = 0.0275);.;.;

MVP

0.71

MPC

1.2

ClinPred

0.99

GERP RS

5.8

Varity_R

0.84

gMVP

0.63

Mutation Taster

=3/97

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over