Genetic Variant RAB11FIP5:p.Asp1211Asn (chr2-73076133-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371272.1(RAB11FIP5):c.3631G>A(p.Asp1211Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

RAB11FIP5
NM_001371272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.16566187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11FIP5	NM_001371272.1 link	c.3631G>A	p.Asp1211Asn	missense_variant	Exon 5 of 6	ENST00000486777.7	NP_001358201.1
RAB11FIP5	NM_015470.3 link	c.1618G>A	p.Asp540Asn	missense_variant	Exon 4 of 5		NP_056285.1	Q9BXF6Q9UFM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAB11FIP5	ENST00000486777.7 link	c.3631G>A	p.Asp1211Asn	missense_variant	Exon 5 of 6	5	NM_001371272.1	ENSP00000489752.1	A0A1B0GTL5
RAB11FIP5	ENST00000258098.6 link	c.1618G>A	p.Asp540Asn	missense_variant	Exon 4 of 5	1		ENSP00000258098.6	Q9BXF6
RAB11FIP5	ENST00000482554.5 link	n.329G>A		non_coding_transcript_exon_variant	Exon 2 of 3	4
RAB11FIP5	ENST00000493523.2 link	n.1527G>A		non_coding_transcript_exon_variant	Exon 3 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251202

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461510

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1111750

Other (OTH)

AF:

0.0000166

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 31, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1618G>A (p.D540N) alteration is located in exon 4 (coding exon 4) of the RAB11FIP5 gene. This alteration results from a G to A substitution at nucleotide position 1618, causing the aspartic acid (D) at amino acid position 540 to be replaced by an asparagine (N). 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

Benign

0.095

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.65

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;L

PhyloP100

3.3

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.084

Sift

Benign

0.23

.;T

Sift4G

Benign

0.38

.;T

Polyphen

0.90

.;P

Vest4

0.19

MVP

0.59

MPC

0.15

ClinPred

0.39

GERP RS

5.3

Varity_R

0.13

gMVP

0.18

Mutation Taster

=88/12

polymorphism

(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.

2-73076133-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