8-37871303-C-T

Variant summary

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

The NM_001002814.3(RAB11FIP1):​c.3499G>A​(p.Ala1167Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,611,142 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: 0.000051 ( 0 hom. )

Consequence

RAB11FIP1
NM_001002814.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.429
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 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=0.14407548).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAB11FIP1NM_001002814.3 linkc.3499G>A p.Ala1167Thr missense_variant Exon 4 of 6 ENST00000330843.9 NP_001002814.2 Q6WKZ4-4
RAB11FIP1XM_017013869.2 linkc.3499G>A p.Ala1167Thr missense_variant Exon 4 of 4 XP_016869358.1
RAB11FIP1NM_025151.5 linkc.1623-775G>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.3499G>A p.Ala1167Thr missense_variant Exon 4 of 6 1 NM_001002814.3 ENSP00000331342.4 Q6WKZ4-4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248256
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
134220
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000294
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:
0.0000267
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000507
AC:
74
AN:
1458822
Hom.:
0
Cov.:
32
AF XY:
0.0000427
AC XY:
31
AN XY:
725770
show subpopulations
Gnomad4 AFR exome
AF:
0.0000600
Gnomad4 AMR exome
AF:
0.0000679
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000558
Gnomad4 OTH exome
AF:
0.0000830
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152320
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3499G>A (p.A1167T) 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 3499, causing the alanine (A) at amino acid position 1167 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
0.068
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0041
T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.078
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.022
D
Polyphen
0.93
P
Vest4
0.076
MutPred
0.14
Gain of glycosylation at A1167 (P = 0.0595);
MVP
0.58
MPC
0.078
ClinPred
0.20
T
GERP RS
0.33
Varity_R
0.11
gMVP
0.079

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: rs755041183; hg19: chr8-37728821; API