19-10118684-G-A

Variant names:

• chr19-10118684-G-A
• NM_003755.5:c.284C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003755.5(EIF3G):​c.284C>T​(p.Ala95Val) variant causes a missense change. 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: 31)
• Consequence: EIF3G NM_003755.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.05

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3041154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3G	NM_003755.5	c.284C>T	p.Ala95Val	missense_variant	Exon 5 of 11	ENST00000253108.9	NP_003746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3G	ENST00000253108.9	c.284C>T	p.Ala95Val	missense_variant	Exon 5 of 11	1	NM_003755.5	ENSP00000253108.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.284C>T (p.A95V) alteration is located in exon 5 (coding exon 5) of the EIF3G gene. This alteration results from a C to T substitution at nucleotide position 284, causing the alanine (A) at amino acid position 95 to be replaced by a valine (V). 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	0.38
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T;.;T;.
Eigen	Benign	0.074
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N;.;.;.
REVEL	Benign	0.099
Sift	Benign	0.20	T;.;.;.
Sift4G	Benign	0.21	T;.;.;.
Polyphen		0.015	B;.;.;.
Vest4		0.38
MutPred		0.22		Gain of methylation at K94 (P = 0.0367);Gain of methylation at K94 (P = 0.0367);Gain of methylation at K94 (P = 0.0367);.;
MVP		0.34
MPC		0.28
ClinPred		0.82	D
GERP RS		5.5
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.16
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-10229360;