Genetic Variant NM_003754.3:c.204T>A (chr11-7987556-T-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_003754.3(EIF3F):c.204T>A(p.Ala68Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,600,298 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

EIF3F
NM_003754.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.118

Publications

0 publications found

Variant links:

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)

EIF3F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 11-7987556-T-A is Benign according to our data. Variant chr11-7987556-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2641576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

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.204T>A	p.Ala68Ala	synonymous	Exon 1 of 8	NP_003745.1	O00303

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3F	ENST00000651655.1	MANE Select	c.204T>A	p.Ala68Ala	synonymous	Exon 1 of 8	ENSP00000499218.1	O00303
EIF3F	ENST00000531572.2	TSL:2	c.204T>A	p.Ala68Ala	synonymous	Exon 1 of 7	ENSP00000434286.2	H0YDT6
EIF3F	ENST00000533626.5	TSL:2	c.204T>A	p.Ala68Ala	synonymous	Exon 3 of 10	ENSP00000431800.1	O00303

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000445

AC:

102

AN:

229212

AF XY:

0.000412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000306

Gnomad ASJ exome

AF:

0.00840

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.000362

GnomAD4 exome

AF:

0.000238

AC:

344

AN:

1448128

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

188

AN XY:

719500

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32762

American (AMR)

AF:

0.000209

AC:

AN:

43076

Ashkenazi Jewish (ASJ)

AF:

0.00843

AC:

214

AN:

25400

East Asian (EAS)

AF:

0.00

AC:

AN:

39340

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52330

Middle Eastern (MID)

AF:

0.000476

AC:

AN:

4200

European-Non Finnish (NFE)

AF:

0.0000542

AC:

AN:

1106860

Other (OTH)

AF:

0.000958

AC:

AN:

59486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000269

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41448

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68028

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000336

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.12

PromoterAI

0.035

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over