EIF3G p.Glu143Asp

Variant names:

• chr19-10116966-C-A
• NM_003755.5:c.429G>T
• EIF3G p.Glu143Asp

Your query was ambiguous. Multiple possible variants found:

• chr19-10116966-C-A
• chr19-10116966-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003755.5(EIF3G):​c.429G>T​(p.Glu143Asp) 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. 14/22 in silico tools predict 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: 32)
• Consequence: EIF3G NM_003755.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.970
• Publications: 0 publications found

Genes affected

EIF3G (HGNC:3274): (eukaryotic translation initiation factor 3 subunit G) This gene encodes a core subunit of the eukaryotic translation initiation factor 3 (eIF3) complex, which is required for initiation of protein translation. An N-terminal caspase cleavage product of the encoded protein may stimulate degradation of DNA. A mutation in this gene is associated with narcolepsy. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15667817).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003755.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3G	NM_003755.5	MANE Select	c.429G>T	p.Glu143Asp	missense	Exon 7 of 11	NP_003746.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3G	ENST00000253108.9	TSL:1 MANE Select	c.429G>T	p.Glu143Asp	missense	Exon 7 of 11	ENSP00000253108.3	O75821
	EIF3G	ENST00000899264.1		c.552G>T	p.Glu184Asp	missense	Exon 8 of 12	ENSP00000569323.1
	EIF3G	ENST00000946252.1		c.471G>T	p.Glu157Asp	missense	Exon 8 of 12	ENSP00000616311.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.97
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.088
Sift	Benign	0.20	T
Sift4G	Benign	0.45	T
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.70
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-10227642;