3-40311531-A-G

Variant names:

• chr3-40311531-A-G
• NM_005875.3:c.257A>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005875.3(EIF1B):​c.257A>G​(p.Gln86Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF1B NM_005875.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.18

Genes affected

EIF1B (HGNC:30792): (eukaryotic translation initiation factor 1B) Enables RNA binding activity. Predicted to be involved in translational initiation. Predicted to be part of eukaryotic 43S preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF1B	NM_005875.3	c.257A>G	p.Gln86Arg	missense_variant	Exon 3 of 4	ENST00000232905.4	NP_005866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF1B	ENST00000232905.4	c.257A>G	p.Gln86Arg	missense_variant	Exon 3 of 4	1	NM_005875.3	ENSP00000232905.3
EIF1B	ENST00000487151.1	n.491A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
EIF1B	ENST00000488260.1	n.373A>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
EIF1B	ENST00000462088.1	n.*17A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.257A>G (p.Q86R) alteration is located in exon 3 (coding exon 3) of the EIF1B gene. This alteration results from a A to G substitution at nucleotide position 257, causing the glutamine (Q) at amino acid position 86 to be replaced by an arginine (R). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Pathogenic	4.0	H
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.82
MutPred		0.89		Loss of ubiquitination at K91 (P = 0.051);
MVP		0.84
MPC		1.5
ClinPred		1.0	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.96

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: chr3-40353022;