11-7987492-C-T

Variant names:

• chr11-7987492-C-T
• rs1942038025
• NM_003754.3:c.140C>T

Variant summary

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

The NM_003754.3(EIF3F):​c.140C>T​(p.Ser47Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF3F NM_003754.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

Genes affected

EIF3F (HGNC:3275): (eukaryotic translation initiation factor 3 subunit F) Enables deubiquitinase activity and identical protein binding activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation; protein deubiquitination; and translational initiation. Located in membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in autosomal recessive non-syndromic intellectual disability. [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=0.09995711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3F	NM_003754.3	c.140C>T	p.Ser47Leu	missense_variant	Exon 1 of 8	ENST00000651655.1	NP_003745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3F	ENST00000651655.1	c.140C>T	p.Ser47Leu	missense_variant	Exon 1 of 8		NM_003754.3	ENSP00000499218.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.140C>T (p.S47L) alteration is located in exon 1 (coding exon 1) of the EIF3F gene. This alteration results from a C to T substitution at nucleotide position 140, causing the serine (S) at amino acid position 47 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T;T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.041	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.68	N;N;.
REVEL	Benign	0.088
Sift	Pathogenic	0.0	D;D;.
Sift4G	Benign	0.12	T;T;.
Polyphen		0.0010	B;B;.
Vest4		0.26
MutPred		0.23		Loss of glycosylation at S47 (P = 2e-04);Loss of glycosylation at S47 (P = 2e-04);Loss of glycosylation at S47 (P = 2e-04);
MVP		0.21
MPC		0.25
ClinPred		0.22	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs1942038025; hg19: chr11-8009039;