Variant 19-10115376-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003755.5(EIF3G):c.947+103C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,338,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000059 ( 0 hom. )

Consequence

EIF3G
NM_003755.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Variant links:

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]

EIF3G links:

EIF3G (HGNC:):

EIF3G links:

P2RY11 (HGNC:8540): (purinergic receptor P2Y11) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is coupled to the stimulation of the phosphoinositide and adenylyl cyclase pathways and behaves as a selective purinoceptor. Naturally occuring read-through transcripts, resulting from intergenic splicing between this gene and an immediately upstream gene (PPAN, encoding peter pan homolog), have been found. The PPAN-P2RY11 read-through mRNA is ubiquitously expressed and encodes a fusion protein that shares identity with each individual gene product. [provided by RefSeq, Jul 2008]

P2RY11 links:

PPAN-P2RY11 (HGNC:33526): (PPAN-P2RY11 readthrough) This locus represents naturally occurring read-through transcription between the adjacent PPAN and P2RY11 genes. Alternative splicing results in two transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. This transcript is found to be ubiquitously expressed and is up-regulated by agents inducing granulocytic differentiation. However, its functional significance in vivo remains unclear. [provided by RefSeq, Nov 2010]

PPAN-P2RY11 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
EIF3G	NM_003755.5 linkuse as main transcript	c.947+103C>G	intron_variant	ENST00000253108.9	NP_003746.2	O75821
P2RY11	NM_002566.5 linkuse as main transcript	c.*638G>C	downstream_gene_variant	ENST00000321826.5	NP_002557.2	Q96G91
PPAN-P2RY11	NM_001040664.3 linkuse as main transcript	c.*638G>C	downstream_gene_variant		NP_001035754.1	Q9NQ55A0A0B4J1V8
PPAN-P2RY11	NM_001198690.2 linkuse as main transcript	c.*1522G>C	downstream_gene_variant		NP_001185619.1	A0A0A6YYI3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
EIF3G	ENST00000253108.9 linkuse as main transcript	c.947+103C>G	intron_variant	1	NM_003755.5	ENSP00000253108.3	O75821
EIF3G	ENST00000593054.5 linkuse as main transcript	c.341+103C>G	intron_variant	5		ENSP00000467187.1	K7EP16
EIF3G	ENST00000590158.1 linkuse as main transcript	n.966+103C>G	intron_variant	2
P2RY11	ENST00000321826.5 linkuse as main transcript	c.*638G>C	downstream_gene_variant	1	NM_002566.5	ENSP00000323872.4	Q96G91

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000590

AC:

AN:

1186082

Hom.:

Cov.:

AF XY:

0.00000681

AC XY:

AN XY:

587292

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000776

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.12

DANN

Benign

0.35

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over