chr9-76392524-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_018339.6(RFK):c.128C>T(p.Ser43Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
RFK
NM_018339.6 missense
NM_018339.6 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 4.04
Genes affected
RFK (HGNC:30324): (riboflavin kinase) Riboflavin kinase (RFK; EC 2.7.1.26) is an essential enzyme that catalyzes the phosphorylation of riboflavin (vitamin B2) to form flavin mononucleotide (FMN), an obligatory step in vitamin B2 utilization and flavin cofactor synthesis (Karthikeyan et al., 2003 [PubMed 12623014]).[supplied by OMIM, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28337008).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFK | NM_018339.6 | c.128C>T | p.Ser43Phe | missense_variant | 2/4 | ENST00000376736.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFK | ENST00000376736.6 | c.128C>T | p.Ser43Phe | missense_variant | 2/4 | 1 | NM_018339.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000123 AC: 31AN: 251454Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135906
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GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461772Hom.: 0 Cov.: 31 AF XY: 0.0000481 AC XY: 35AN XY: 727198
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152276Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74470
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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 29, 2022 | The c.128C>T (p.S43F) alteration is located in exon 2 (coding exon 2) of the RFK gene. This alteration results from a C to T substitution at nucleotide position 128, causing the serine (S) at amino acid position 43 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
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