1-161001112-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_016946.6(F11R):c.149G>A(p.Cys50Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
F11R
NM_016946.6 missense
NM_016946.6 missense
Scores
4
8
3
Clinical Significance
Conservation
PhyloP100: 3.77
Genes affected
F11R (HGNC:14685): (F11 receptor) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. The protein encoded by this immunoglobulin superfamily gene member is an important regulator of tight junction assembly in epithelia. In addition, the encoded protein can act as (1) a receptor for reovirus, (2) a ligand for the integrin LFA1, involved in leukocyte transmigration, and (3) a platelet receptor. Multiple 5' alternatively spliced variants, encoding the same protein, have been identified but their biological validity has not been established. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.977
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F11R | NM_016946.6 | c.149G>A | p.Cys50Tyr | missense_variant | 3/10 | ENST00000368026.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F11R | ENST00000368026.11 | c.149G>A | p.Cys50Tyr | missense_variant | 3/10 | 1 | NM_016946.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152100Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251396Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135886
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GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461842Hom.: 0 Cov.: 32 AF XY: 0.0000454 AC XY: 33AN XY: 727224
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74434
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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 | Nov 03, 2022 | The c.149G>A (p.C50Y) alteration is located in exon 3 (coding exon 3) of the F11R gene. This alteration results from a G to A substitution at nucleotide position 149, causing the cysteine (C) at amino acid position 50 to be replaced by a tyrosine (Y). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;.
Vest4
MutPred
Gain of phosphorylation at C50 (P = 0.0395);Gain of phosphorylation at C50 (P = 0.0395);Gain of phosphorylation at C50 (P = 0.0395);
MVP
MPC
1.1
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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