11-32596038-G-C

Variant names:

• chr11-32596038-G-C
• rs1258414084
• NM_006360.6:c.790G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006360.6(EIF3M):​c.790G>C​(p.Asp264His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF3M NM_006360.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42049015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3M	NM_006360.6	c.790G>C	p.Asp264His	missense_variant	Exon 8 of 11	ENST00000531120.6	NP_006351.2
EIF3M	NM_001307929.2	c.394G>C	p.Asp132His	missense_variant	Exon 5 of 8		NP_001294858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3M	ENST00000531120.6	c.790G>C	p.Asp264His	missense_variant	Exon 8 of 11	1	NM_006360.6	ENSP00000436049.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.790G>C (p.D264H) alteration is located in exon 8 (coding exon 8) of the EIF3M gene. This alteration results from a G to C substitution at nucleotide position 790, causing the aspartic acid (D) at amino acid position 264 to be replaced by a histidine (H). 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	0.37
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T;.;T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.080	T;T;T
Polyphen		0.77	P;.;.
Vest4		0.61
MutPred		0.30		Gain of catalytic residue at L266 (P = 0.0473);.;.;
MVP		0.24
MPC		0.89
ClinPred		0.92	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.59
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1258414084; hg19: chr11-32617584;