3-40311531-A-G

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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]

ENTPD3-AS1 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005875.3. 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
	EIF1B	NM_005875.3	MANE Select	c.257A>G	p.Gln86Arg	missense	Exon 3 of 4	NP_005866.1	O60739

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF1B	ENST00000232905.4	TSL:1 MANE Select	c.257A>G	p.Gln86Arg	missense	Exon 3 of 4	ENSP00000232905.3	O60739
	EIF1B	ENST00000487151.1	TSL:2	n.491A>G		non_coding_transcript_exon	Exon 2 of 2
	EIF1B	ENST00000488260.1	TSL:2	n.373A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		9.2
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
Mutation Taster		=58/42	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

Other links and lift over

hg19: chr3-40353022;