2-73076181-G-A

Position:

chr2-73076181-G-A

Variant summary

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

The NM_001371272.1(RAB11FIP5):c.3583C>T(p.Pro1195Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000668 in 1,601,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

RAB11FIP5
NM_001371272.1 missense, splice_region

Scores

Splicing: ADA: 0.1202

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

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:

RAB11FIP5 (HGNC:):

RAB11FIP5 links:

Genome browser will be placed here

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=0.20265242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB11FIP5	NM_001371272.1 linkuse as main transcript	c.3583C>T	p.Pro1195Ser	missense_variant, splice_region_variant	5/6	ENST00000486777.7	NP_001358201.1
RAB11FIP5	NM_015470.3 linkuse as main transcript	c.1570C>T	p.Pro524Ser	missense_variant, splice_region_variant	4/5		NP_056285.1	Q9BXF6Q9UFM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAB11FIP5	ENST00000486777.7 linkuse as main transcript	c.3583C>T	p.Pro1195Ser	missense_variant, splice_region_variant	5/6	5	NM_001371272.1	ENSP00000489752.1	A0A1B0GTL5
RAB11FIP5	ENST00000258098.6 linkuse as main transcript	c.1570C>T	p.Pro524Ser	missense_variant, splice_region_variant	4/5	1		ENSP00000258098.6	Q9BXF6
RAB11FIP5	ENST00000482554.5 linkuse as main transcript	n.281C>T		splice_region_variant, non_coding_transcript_exon_variant	2/3	4
RAB11FIP5	ENST00000493523.2 linkuse as main transcript	n.1479C>T		splice_region_variant, non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152226

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

248680

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000976

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000718

AC:

104

AN:

1449368

Hom.:

Cov.:

AF XY:

0.0000776

AC XY:

AN XY:

721498

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000916

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000808

Hom.:

Bravo

AF:

0.0000264

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000297

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

Oct 28, 2024

The c.1570C>T (p.P524S) alteration is located in exon 4 (coding exon 4) of the RAB11FIP5 gene. This alteration results from a C to T substitution at nucleotide position 1570, causing the proline (P) at amino acid position 524 to be replaced by a serine (S). 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

0.44

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;D

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

.;L

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.0

.;D

REVEL

Benign

0.086

Sift

Uncertain

0.012

.;D

Sift4G

Benign

0.29

.;T

Polyphen

0.89

.;P

Vest4

0.28

MVP

0.65

MPC

0.12

ClinPred

0.32

GERP RS

4.4

Varity_R

0.27

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.12

dbscSNV1_RF

Benign

0.51

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