19-10119852-G-T

Variant names:

• chr19-10119852-G-T
• rs776642037
• NM_003755.5:c.8C>A

Variant summary

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

The NM_003755.5(EIF3G):​c.8C>A​(p.Thr3Asn) 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. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T3I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF3G NM_003755.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01
• Publications: 2 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30721873).

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.8C>A	p.Thr3Asn	missense	Exon 1 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.8C>A	p.Thr3Asn	missense	Exon 1 of 11	ENSP00000253108.3	O75821
	EIF3G	ENST00000899264.1		c.8C>A	p.Thr3Asn	missense	Exon 1 of 12	ENSP00000569323.1
	EIF3G	ENST00000946252.1		c.8C>A	p.Thr3Asn	missense	Exon 1 of 12	ENSP00000616311.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.051	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.15
Sift	Uncertain	0.015	D
Sift4G	Benign	0.20	T
Polyphen		0.28	B
Vest4		0.53
MutPred		0.093		Loss of glycosylation at T3 (P = 0.0102)
MVP		0.42
MPC		0.32
ClinPred		0.80	D
GERP RS		4.7
PromoterAI		0.071	Neutral
Varity_R		0.24
gMVP		0.28
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776642037; hg19: chr19-10230528;