8-37871396-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001002814.3(RAB11FIP1):​c.3406G>A​(p.Ala1136Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000065 in 1,614,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

RAB11FIP1
NM_001002814.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.205
Variant links:
Genes affected
RAB11FIP1 (HGNC:30265): (RAB11 family interacting protein 1) This gene encodes one of the Rab11-family interacting proteins (Rab11-FIPs), which play a role in the Rab-11 mediated recycling of vesicles. The encoded protein may be involved in endocytic sorting, trafficking of proteins including integrin subunits and epidermal growth factor receptor (EGFR), and transport between the recycling endosome and the trans-Golgi network. Alternative splicing results in multiple transcript variants. A pseudogene is described on the X chromosome. [provided by RefSeq, Dec 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.025794595).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB11FIP1NM_001002814.3 linkc.3406G>A p.Ala1136Thr missense_variant Exon 4 of 6 ENST00000330843.9 NP_001002814.2 Q6WKZ4-4
RAB11FIP1XM_017013869.2 linkc.3406G>A p.Ala1136Thr missense_variant Exon 4 of 4 XP_016869358.1
RAB11FIP1NM_025151.5 linkc.1623-868G>A intron_variant Intron 3 of 4 NP_079427.4 Q6WKZ4-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAB11FIP1ENST00000330843.9 linkc.3406G>A p.Ala1136Thr missense_variant Exon 4 of 6 1 NM_001002814.3 ENSP00000331342.4 Q6WKZ4-4

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152214
Hom.:
0
Cov.:
32
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:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000716
AC:
18
AN:
251462
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000629
AC:
92
AN:
1461892
Hom.:
0
Cov.:
32
AF XY:
0.0000743
AC XY:
54
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000719
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000853
AC:
13
AN:
152332
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000109
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.00
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
Nov 30, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3406G>A (p.A1136T) alteration is located in exon 4 (coding exon 4) of the RAB11FIP1 gene. This alteration results from a G to A substitution at nucleotide position 3406, causing the alanine (A) at amino acid position 1136 to be replaced by a threonine (T). 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
0.088
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
15
DANN
Benign
0.92
DEOGEN2
Benign
0.0023
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.34
N
REVEL
Benign
0.093
Sift
Benign
0.49
T
Sift4G
Benign
0.72
T
Polyphen
0.41
B
Vest4
0.023
MVP
0.43
MPC
0.14
ClinPred
0.054
T
GERP RS
0.051
Varity_R
0.036
gMVP
0.077

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.

Other links and lift over

dbSNP: rs201773104; hg19: chr8-37728914; API