11-7987371-C-T

Variant names:

• chr11-7987371-C-T
• rs200048982
• NM_003754.3:c.19C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003754.3(EIF3F):​c.19C>T​(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,595,852 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P7P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: EIF3F NM_003754.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0067661107).
• BP6: Variant 11-7987371-C-T is Benign according to our data. Variant chr11-7987371-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2342515.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3F	NM_003754.3	c.19C>T	p.Pro7Ser	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.19C>T	p.Pro7Ser	missense_variant	Exon 1 of 8		NM_003754.3	ENSP00000499218.1

Frequencies

GnomAD3 genomes AF: 0.000282 AC: 43 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000371 AC: 85 AN: 228948 Hom.: 0 AF XY: 0.000490 AC XY: 62 AN XY: 126480

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00277

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00113

Gnomad FIN exome AF: 0.000158

Gnomad NFE exome AF: 0.000199

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.000258 AC: 372 AN: 1443632 Hom.: 1 Cov.: 30 AF XY: 0.000336 AC XY: 241 AN XY: 718170

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.0000452

Gnomad4 ASJ exome AF: 0.00277

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00157

Gnomad4 FIN exome AF: 0.000229

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.000499

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21 AN XY: 74370

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000956

Alfa AF: 0.000386 Hom.: 0

Bravo AF: 0.000174

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000267 AC: 2

ExAC AF: 0.000389 AC: 46

EpiCase AF: 0.000436

EpiControl AF: 0.000297

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Dec 06, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.32
DANN	Benign	0.88
DEOGEN2	Benign	0.012	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0091	N
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.0068	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.48	N;N;.
REVEL	Benign	0.011
Sift	Pathogenic	0.0	D;D;.
Sift4G	Benign	0.11	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.095
MVP		0.082
MPC		0.28
ClinPred		0.042	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.25

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: rs200048982; hg19: chr11-8008918;