NM_198241.3:c.481A>C

Variant names:

• chr3-184319745-A-C
• rs13319149
• NM_198241.3:c.481A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198241.3(EIF4G1):​c.481A>C​(p.Thr161Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. T161A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EIF4G1 NM_198241.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747

Genes affected

EIF4G1 (HGNC:3296): (eukaryotic translation initiation factor 4 gamma 1) The protein encoded by this gene is a component of the multi-subunit protein complex EIF4F. This complex facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. The recognition of the mRNA cap and the ATP-dependent unwinding of 5'-terminal secondary structure is catalyzed by factors in this complex. The subunit encoded by this gene is a large scaffolding protein that contains binding sites for other members of the EIF4F complex. A domain at its N-terminus can also interact with the poly(A)-binding protein, which may mediate the circularization of mRNA during translation. Alternative splicing results in multiple transcript variants, some of which are derived from alternative promoter usage. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0556913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4G1	NM_198241.3	c.481A>C	p.Thr161Pro	missense_variant	Exon 7 of 33	ENST00000346169.7	NP_937884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4G1	ENST00000346169.7	c.481A>C	p.Thr161Pro	missense_variant	Exon 7 of 33	1	NM_198241.3	ENSP00000316879.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.083	T;.;.;.;.;T;.;T;.;T;.;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.21	T;T;T;T;T;T;.;T;T;T;T;.;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.056	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N;.;.;.;.;.;.;.;.;.;N;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.86	N;N;N;N;N;N;N;N;.;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.34	T;T;T;T;T;T;T;T;.;T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0010	B;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.16
MutPred		0.21		Gain of catalytic residue at P160 (P = 0.0168);.;.;.;Gain of catalytic residue at P160 (P = 0.0168);.;.;.;.;.;Gain of catalytic residue at P160 (P = 0.0168);.;.;.;
MVP		0.27
MPC		0.88
ClinPred		0.11	T
GERP RS		-1.8
Varity_R		0.19
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13319149; hg19: chr3-184037533;