Variant chr10-118039236-C-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_014904.3(RAB11FIP2):c.1001G>T(p.Ser334Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

RAB11FIP2
NM_014904.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

RAB11FIP2 (HGNC:29152): (RAB11 family interacting protein 2) Enables protein homodimerization activity and protein kinase binding activity. Involved in several processes, including TRAM-dependent toll-like receptor 4 signaling pathway; phagocytosis; and positive regulation of GTPase activity. Located in endosome; nucleoplasm; and phagocytic cup. [provided by Alliance of Genome Resources, Apr 2022]

RAB11FIP2 links:

(HGNC:):

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=0.12890607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB11FIP2	NM_014904.3 linkuse as main transcript	c.1001G>T	p.Ser334Ile	missense_variant	3/5	ENST00000355624.8	NP_055719.1
RAB11FIP2	NM_001330167.2 linkuse as main transcript	c.1001G>T	p.Ser334Ile	missense_variant	3/6		NP_001317096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB11FIP2	ENST00000355624.8 linkuse as main transcript	c.1001G>T	p.Ser334Ile	missense_variant	3/5	1	NM_014904.3	ENSP00000347839	P1	Q7L804-1
RAB11FIP2	ENST00000369199.5 linkuse as main transcript	c.1001G>T	p.Ser334Ile	missense_variant	3/6	1		ENSP00000358200		Q7L804-2
	ENST00000451610.6 linkuse as main transcript	n.164-910C>A		intron_variant, non_coding_transcript_variant		2
RAB11FIP2	ENST00000483413.1 linkuse as main transcript	n.395G>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250960

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135620

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:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461548

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727076

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

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

Nov 08, 2022

The c.1001G>T (p.S334I) alteration is located in exon 3 (coding exon 3) of the RAB11FIP2 gene. This alteration results from a G to T substitution at nucleotide position 1001, causing the serine (S) at amino acid position 334 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

0.85

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.085

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.043

D;D

Polyphen

0.055

B;.

Vest4

0.28

MVP

0.28

MPC

0.16

ClinPred

0.33

GERP RS

5.8

Varity_R

0.16

gMVP

0.15

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