Genetic Variant RAB11FIP5:p.Arg1285Gln (chr2-73075642-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001371272.1(RAB11FIP5):c.3854G>A(p.Arg1285Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000333 in 1,613,878 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

RAB11FIP5
NM_001371272.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.07

Publications

0 publications found

Variant links:

Genes affected

RAB11FIP5 (HGNC:24845): (RAB11 family interacting protein 5) Enables gamma-tubulin binding activity. Involved in cellular response to acidic pH; negative regulation of adiponectin secretion; and regulation of protein localization to cell surface. Located in centriolar satellite and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB11FIP5 links:

SFXN5 (HGNC:16073): (sideroflexin 5) Predicted to enable citrate transmembrane transporter activity. Predicted to be involved in citrate transport and mitochondrial transmembrane transport. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SFXN5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005943984).

BP6

Variant 2-73075642-C-T is Benign according to our data. Variant chr2-73075642-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3051484.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11FIP5	NM_001371272.1 link	c.3854G>A	p.Arg1285Gln	missense_variant	Exon 6 of 6	ENST00000486777.7	NP_001358201.1
RAB11FIP5	NM_015470.3 link	c.1841G>A	p.Arg614Gln	missense_variant	Exon 5 of 5		NP_056285.1	Q9BXF6Q9UFM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB11FIP5	ENST00000486777.7 link	c.3854G>A	p.Arg1285Gln	missense_variant	Exon 6 of 6	5	NM_001371272.1	ENSP00000489752.1		A0A1B0GTL5

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

279

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00647

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000448

AC:

111

AN:

247810

AF XY:

0.000365

show subpopulations

Gnomad AFR exome

AF:

0.00597

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000177

AC:

258

AN:

1461578

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

112

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00627

AC:

210

AN:

33476

American (AMR)

AF:

0.000269

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39672

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111892

Other (OTH)

AF:

0.000348

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00183

AC:

279

AN:

152300

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

118

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00645

AC:

268

AN:

41568

American (AMR)

AF:

0.000588

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000578

Hom.:

Bravo

AF:

0.00205

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000527

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RAB11FIP5-related disorder

Benign:1

Feb 03, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

PhyloP100

1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

0.14

.;N

REVEL

Benign

0.13

Sift

Benign

0.15

.;T

Sift4G

Benign

0.41

.;T

Polyphen

0.98

.;D

Vest4

0.19

MVP

0.51

MPC

0.58

ClinPred

0.027

GERP RS

4.2

Varity_R

0.029

gMVP

0.27

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-73075642-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over