NM_006360.6:c.1080T>A

Variant names:

• chr11-32602354-T-A
• rs139971850
• NM_006360.6:c.1080T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006360.6(EIF3M):​c.1080T>A​(p.Asn360Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,612,566 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: EIF3M NM_006360.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• Publications: 1 publications found

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040208876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3M	NM_006360.6	c.1080T>A	p.Asn360Lys	missense_variant	Exon 11 of 11	ENST00000531120.6	NP_006351.2
EIF3M	NM_001307929.2	c.684T>A	p.Asn228Lys	missense_variant	Exon 8 of 8		NP_001294858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3M	ENST00000531120.6	c.1080T>A	p.Asn360Lys	missense_variant	Exon 11 of 11	1	NM_006360.6	ENSP00000436049.1
EIF3M	ENST00000524896.5	c.684T>A	p.Asn228Lys	missense_variant	Exon 8 of 8	2		ENSP00000436787.1
EIF3M	ENST00000526267.1	c.639T>A	p.Asn213Lys	missense_variant	Exon 8 of 8	2		ENSP00000432139.1
EIF3M	ENST00000525054.1	n.*52T>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152000 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000327 AC: 82 AN: 251134 AF XY: 0.000412

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000220 AC: 322 AN: 1460448 Hom.: 1 Cov.: 30 AF XY: 0.000267 AC XY: 194 AN XY: 726544

African (AFR) AF: 0.0000299 AC: 1 AN: 33440

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00113 AC: 97 AN: 86074

European-Finnish (FIN) AF: 0.0000750 AC: 4 AN: 53350

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5760

European-Non Finnish (NFE) AF: 0.000176 AC: 196 AN: 1111140

Other (OTH) AF: 0.000216 AC: 13 AN: 60320

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152118 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.000131 AC: 2 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000236 AC: 16 AN: 67916

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000313 Hom.: 0

Bravo AF: 0.000170

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000346 AC: 42

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1080T>A (p.N360K) alteration is located in exon 11 (coding exon 11) of the EIF3M gene. This alteration results from a T to A substitution at nucleotide position 1080, causing the asparagine (N) at amino acid position 360 to be replaced by a lysine (K). 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	0.78
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.;.
PhyloP100		1.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.10
Sift	Uncertain	0.018	D;D;D
Sift4G	Uncertain	0.025	D;D;D
Polyphen		0.90	P;.;.
Vest4		0.76
MutPred		0.33		Loss of ubiquitination at K365 (P = 0.0334);.;.;
MVP		0.38
MPC		0.82
ClinPred		0.16	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.70
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs139971850; hg19: chr11-32623900;