17-31528737-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_032932.6(RAB11FIP4):c.1612C>T(p.Arg538Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00019 in 1,611,232 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 1 hom. )
Consequence
RAB11FIP4
NM_032932.6 missense
NM_032932.6 missense
Scores
4
9
3
Clinical Significance
Conservation
PhyloP100: 3.90
Genes affected
RAB11FIP4 (HGNC:30267): (RAB11 family interacting protein 4) The protein encoded by this gene interacts with RAB11 and is thought to be involved in bringing recycling endosome membranes to the cleavage furrow in late cytokinesis. Hypoxic conditions can lead to an upregulation of the encoded protein and enhance the metastatic potential of hepatocellular carcinoma. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.756
BS2
?
High AC in GnomAd at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAB11FIP4 | NM_032932.6 | c.1612C>T | p.Arg538Cys | missense_variant | 13/15 | ENST00000621161.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAB11FIP4 | ENST00000621161.5 | c.1612C>T | p.Arg538Cys | missense_variant | 13/15 | 1 | NM_032932.6 | P1 | |
RAB11FIP4 | ENST00000394744.6 | c.1306C>T | p.Arg436Cys | missense_variant | 11/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152236Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000607 AC: 15AN: 247010Hom.: 0 AF XY: 0.0000671 AC XY: 9AN XY: 134166
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GnomAD4 exome AF: 0.000201 AC: 293AN: 1458996Hom.: 1 Cov.: 32 AF XY: 0.000203 AC XY: 147AN XY: 725774
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74368
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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 | Jun 18, 2021 | The c.1612C>T (p.R538C) alteration is located in exon 13 (coding exon 13) of the RAB11FIP4 gene. This alteration results from a C to T substitution at nucleotide position 1612, causing the arginine (R) at amino acid position 538 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Benign
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at