11-32602354-T-G

Variant names:

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

Variant summary

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

The NM_006360.6(EIF3M):​c.1080T>G​(p.Asn360Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF3M NM_006360.6 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.29319978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3M	NM_006360.6	c.1080T>G	p.Asn360Lys	missense_variant	Exon 11 of 11	ENST00000531120.6	NP_006351.2
EIF3M	NM_001307929.2	c.684T>G	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>G	p.Asn360Lys	missense_variant	Exon 11 of 11	1	NM_006360.6	ENSP00000436049.1
EIF3M	ENST00000524896.5	c.684T>G	p.Asn228Lys	missense_variant	Exon 8 of 8	2		ENSP00000436787.1
EIF3M	ENST00000526267.1	c.639T>G	p.Asn213Lys	missense_variant	Exon 8 of 8	2		ENSP00000432139.1
EIF3M	ENST00000525054.1	n.*52T>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.14	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	0.89	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.29	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		0.97	D
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)		0.020		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;