11-7987399-C-T

Variant names:

• chr11-7987399-C-T
• NM_003754.3:c.47C>T

Variant summary

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

The NM_003754.3(EIF3F):​c.47C>T​(p.Thr16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,448,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: EIF3F NM_003754.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00300

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 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=0.06415874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3F	NM_003754.3	c.47C>T	p.Thr16Ile	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.47C>T	p.Thr16Ile	missense_variant	Exon 1 of 8		NM_003754.3	ENSP00000499218.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1448212 Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3 AN XY: 720890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47C>T (p.T16I) 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 47, causing the threonine (T) at amino acid position 16 to be replaced by an isoleucine (I). 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	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.82
DEOGEN2	Benign	0.0049	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.064	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.050	N;N;.
REVEL	Benign	0.040
Sift	Benign	0.13	T;T;.
Sift4G	Benign	0.12	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.15
MutPred		0.25		Loss of glycosylation at T16 (P = 1e-04);Loss of glycosylation at T16 (P = 1e-04);Loss of glycosylation at T16 (P = 1e-04);
MVP		0.082
MPC		0.30
ClinPred		0.052	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.21

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: chr11-8008946;