Variant 2-73075628-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371272.1(RAB11FIP5):c.3868C>T(p.Arg1290Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1290Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RAB11FIP5
NM_001371272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24523741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB11FIP5	NM_001371272.1 linkuse as main transcript	c.3868C>T	p.Arg1290Trp	missense_variant	6/6	ENST00000486777.7
RAB11FIP5	NM_015470.3 linkuse as main transcript	c.1855C>T	p.Arg619Trp	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB11FIP5	ENST00000486777.7 linkuse as main transcript	c.3868C>T	p.Arg1290Trp	missense_variant	6/6	5	NM_001371272.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.1855C>T (p.R619W) alteration is located in exon 5 (coding exon 5) of the RAB11FIP5 gene. This alteration results from a C to T substitution at nucleotide position 1855, causing the arginine (R) at amino acid position 619 to be replaced by a tryptophan (W). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;D

Eigen

Benign

-0.012

Eigen_PC

Benign

-0.071

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.075

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.34

.;N

MutationTaster

Benign

0.71

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.9

.;D

REVEL

Benign

0.14

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0060

.;D

Polyphen

1.0

.;D

Vest4

0.31

MutPred

0.50

.;Loss of disorder (P = 0.0106);

MVP

0.64

MPC

0.46

ClinPred

0.96

GERP RS

3.2

Varity_R

0.16

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over