11-7987504-C-G

Variant names:

• chr11-7987504-C-G
• rs1408869615
• NM_003754.3:c.152C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003754.3(EIF3F):​c.152C>G​(p.Ala51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 6.9e-7 (0 hom.)
• Consequence: EIF3F NM_003754.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.515
• Publications: 0 publications found

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]

EIF3F Gene-Disease associations (from GenCC):

• syndromic intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder, autosomal recessive 67

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09291655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003754.3. 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
	EIF3F	NM_003754.3	MANE Select	c.152C>G	p.Ala51Gly	missense	Exon 1 of 8	NP_003745.1	O00303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3F	ENST00000651655.1	MANE Select	c.152C>G	p.Ala51Gly	missense	Exon 1 of 8	ENSP00000499218.1	O00303
	EIF3F	ENST00000531572.2	TSL:2	c.152C>G	p.Ala51Gly	missense	Exon 1 of 7	ENSP00000434286.2	H0YDT6
	EIF3F	ENST00000533626.5	TSL:2	c.152C>G	p.Ala51Gly	missense	Exon 3 of 10	ENSP00000431800.1	O00303

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000429 AC: 1 AN: 233020 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453632 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722764

African (AFR) AF: 0.00 AC: 0 AN: 33142

American (AMR) AF: 0.0000225 AC: 1 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 85698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4496

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109660

Other (OTH) AF: 0.00 AC: 0 AN: 59868

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.055	N
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.52
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.087
Sift	Uncertain	0.016	D
Sift4G	Benign	0.087	T
Polyphen		0.0020	B
Vest4		0.27
MutPred		0.18		Loss of glycosylation at P49 (P = 0.0874)
MVP		0.35
MPC		0.28
ClinPred		0.11	T
GERP RS		2.1
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.22
Mutation Taster		=99/1	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

dbSNP: rs1408869615; hg19: chr11-8009051;