chr11-92353781-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001367949.2(FAT3):c.1669C>T(p.Arg557Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,461,262 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: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
FAT3
NM_001367949.2 missense
NM_001367949.2 missense
Scores
10
5
2
Clinical Significance
Conservation
PhyloP100: 6.24
Genes affected
FAT3 (HGNC:23112): (FAT atypical cadherin 3) Predicted to enable calcium ion binding activity. Predicted to be involved in cell-cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of dendrite development; neuron migration; and retina layer formation. Predicted to be located in dendrite and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.878
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAT3 | NM_001367949.2 | c.1669C>T | p.Arg557Cys | missense_variant | 2/28 | ENST00000525166.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAT3 | ENST00000525166.6 | c.1669C>T | p.Arg557Cys | missense_variant | 2/28 | 5 | NM_001367949.2 | ||
FAT3 | ENST00000409404.6 | c.1669C>T | p.Arg557Cys | missense_variant | 1/25 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248530Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134798
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GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461262Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726826
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
Bravo
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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 | May 10, 2022 | The c.1669C>T (p.R557C) alteration is located in exon 1 (coding exon 1) of the FAT3 gene. This alteration results from a C to T substitution at nucleotide position 1669, causing the arginine (R) at amino acid position 557 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Vest4
MutPred
Loss of disorder (P = 0.0115);.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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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