7-2355063-A-C

Variant names:

• chr7-2355063-A-C
• rs927045802
• NM_001037283.2:c.142A>C
• EIF3B p.Thr48Pro

Variant summary

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

The NM_001037283.2(EIF3B):​c.142A>C​(p.Thr48Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000916 in 1,092,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. T48I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 0 publications found

Genes affected

EIF3B (HGNC:3280): (eukaryotic translation initiation factor 3 subunit B) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.082680434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037283.2. 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
	EIF3B	NM_001037283.2	MANE Select	c.142A>C	p.Thr48Pro	missense	Exon 1 of 19	NP_001032360.1	P55884-1
	EIF3B	NM_001362791.2		c.142A>C	p.Thr48Pro	missense	Exon 1 of 19	NP_001349720.1	P55884-1
	EIF3B	NM_003751.4		c.142A>C	p.Thr48Pro	missense	Exon 1 of 19	NP_003742.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3B	ENST00000360876.9	TSL:1 MANE Select	c.142A>C	p.Thr48Pro	missense	Exon 1 of 19	ENSP00000354125.4	P55884-1
	EIF3B	ENST00000397011.2	TSL:1	c.142A>C	p.Thr48Pro	missense	Exon 1 of 19	ENSP00000380206.2	P55884-1
	EIF3B	ENST00000899983.1		c.142A>C	p.Thr48Pro	missense	Exon 1 of 19	ENSP00000570042.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.16e-7 AC: 1 AN: 1092008 Hom.: 0 Cov.: 29 AF XY: 0.00000192 AC XY: 1 AN XY: 520162

African (AFR) AF: 0.00 AC: 0 AN: 22480

American (AMR) AF: 0.00 AC: 0 AN: 8014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14040

East Asian (EAS) AF: 0.00 AC: 0 AN: 25422

South Asian (SAS) AF: 0.00 AC: 0 AN: 27554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2908

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 926064

Other (OTH) AF: 0.00 AC: 0 AN: 43438

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.38
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.10
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.067
Sift	Uncertain	0.027	D
Sift4G	Benign	0.32	T
PromoterAI		0.047	Neutral
Varity_R		0.061
gMVP		0.11
Mutation Taster		=91/9	polymorphism

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

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

Other links and lift over

dbSNP: rs927045802;

hg19: chr7-2394698;