7-2355045-G-T

Variant names:

• chr7-2355045-G-T
• NM_001037283.2:c.124G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037283.2(EIF3B):​c.124G>T​(p.Ala42Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,060,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.27

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07532483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3B	NM_001037283.2	c.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 19	ENST00000360876.9	NP_001032360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3B	ENST00000360876.9	c.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 19	1	NM_001037283.2	ENSP00000354125.4
EIF3B	ENST00000397011.2	c.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 19	1		ENSP00000380206.2
EIF3B	ENST00000413917.5	c.124G>T	p.Ala42Ser	missense_variant	Exon 1 of 7	2		ENSP00000407785.1
EIF3B	ENST00000431643.5	c.-504-189G>T		intron_variant	Intron 1 of 7	5		ENSP00000408062.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000283 AC: 3 AN: 1060270 Hom.: 0 Cov.: 29 AF XY: 0.00000399 AC XY: 2 AN XY: 501608

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: 0.00000331

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.124G>T (p.A42S) alteration is located in exon 1 (coding exon 1) of the EIF3B gene. This alteration results from a G to T substitution at nucleotide position 124, causing the alanine (A) at amino acid position 42 to be replaced by a serine (S). 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	Benign	0.082
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.75
DEOGEN2	Benign	0.019	T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.41	.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.075	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.044
Sift	Benign	0.032	D;T;D
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.079
MutPred		0.19		Gain of phosphorylation at A42 (P = 0.0041);Gain of phosphorylation at A42 (P = 0.0041);Gain of phosphorylation at A42 (P = 0.0041);
MVP		0.29
MPC		0.34
ClinPred		0.030	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.072
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-2394680;