12-53019940-A-G

Variant names:

• chr12-53019940-A-G
• NM_001417.7:c.391A>G

Variant summary

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

The NM_001417.7(EIF4B):​c.391A>G​(p.Ser131Gly) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: EIF4B NM_001417.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.30

Genes affected

EIF4B (HGNC:3285): (eukaryotic translation initiation factor 4B) Enables RNA binding activity. Predicted to be involved in eukaryotic translation initiation factor 4F complex assembly and formation of translation preinitiation complex. Located in cytosol. Biomarker of autism spectrum disorder and major depressive disorder. [provided by Alliance of Genome Resources, Apr 2022]

TNS2-AS1 (HGNC:27464): (TNS2 antisense RNA 1)

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=0.2189731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4B	NM_001417.7	c.391A>G	p.Ser131Gly	missense_variant	Exon 4 of 15	ENST00000262056.14	NP_001408.2
EIF4B	NM_001300821.3	c.391A>G	p.Ser131Gly	missense_variant	Exon 4 of 15		NP_001287750.1
EIF4B	NM_001330654.2	c.360+934A>G		intron_variant	Intron 3 of 13		NP_001317583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4B	ENST00000262056.14	c.391A>G	p.Ser131Gly	missense_variant	Exon 4 of 15	1	NM_001417.7	ENSP00000262056.9

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.391A>G (p.S131G) alteration is located in exon 4 (coding exon 4) of the EIF4B gene. This alteration results from a A to G substitution at nucleotide position 391, causing the serine (S) at amino acid position 131 to be replaced by a glycine (G). 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	0.19
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.063	T;T;.;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	-0.25	N;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.040	N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.59	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0010	B;.;B;.;.
Vest4		0.20
MutPred		0.41		Gain of catalytic residue at L136 (P = 2e-04);.;Gain of catalytic residue at L136 (P = 2e-04);Gain of catalytic residue at L136 (P = 2e-04);Gain of catalytic residue at L136 (P = 2e-04);
MVP		0.80
MPC		0.80
ClinPred		0.64	D
GERP RS		3.5
Varity_R		0.079
gMVP		0.28

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: chr12-53413724;