14-74734911-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015962.5(FCF1):c.578A>T(p.Tyr193Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
FCF1
NM_015962.5 missense
NM_015962.5 missense
Scores
1
3
15
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.49
Genes affected
FCF1 (HGNC:20220): (FCF1 rRNA-processing protein) Enables RNA binding activity. Predicted to be involved in rRNA processing. Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.15756044).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FCF1 | NM_015962.5 | c.578A>T | p.Tyr193Phe | missense_variant | 8/8 | ENST00000341162.8 | |
FCF1 | NM_001318508.2 | c.542A>T | p.Tyr181Phe | missense_variant | 8/8 | ||
FCF1 | XM_011536815.4 | c.506A>T | p.Tyr169Phe | missense_variant | 7/7 | ||
FCF1 | XM_011536816.4 | c.470A>T | p.Tyr157Phe | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FCF1 | ENST00000341162.8 | c.578A>T | p.Tyr193Phe | missense_variant | 8/8 | 1 | NM_015962.5 | P1 | |
FCF1 | ENST00000534938.6 | c.542A>T | p.Tyr181Phe | missense_variant | 8/8 | 3 | |||
FCF1 | ENST00000553615.5 | c.533A>T | p.Tyr178Phe | missense_variant | 8/8 | 3 | |||
FCF1 | ENST00000556814.5 | c.*337A>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/8 | 4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461650Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4AN XY: 727140
GnomAD4 exome
AF:
AC:
5
AN:
1461650
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Cov.:
29
AF XY:
AC XY:
4
AN XY:
727140
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;B
Vest4
MutPred
Loss of phosphorylation at Y193 (P = 0.0178);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at