rs1477068520
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014334.4(FRRS1L):āc.53T>Gā(p.Leu18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000762 in 1,180,502 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L18L) has been classified as Likely benign.
Frequency
Consequence
NM_014334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRRS1L | NM_014334.4 | c.53T>G | p.Leu18Arg | missense_variant | 1/5 | ENST00000561981.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRRS1L | ENST00000561981.5 | c.53T>G | p.Leu18Arg | missense_variant | 1/5 | 1 | NM_014334.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000543 AC: 8AN: 147358Hom.: 0 Cov.: 25
GnomAD4 exome AF: 9.68e-7 AC: 1AN: 1033144Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 494694
GnomAD4 genome ? AF: 0.0000543 AC: 8AN: 147358Hom.: 0 Cov.: 25 AF XY: 0.0000418 AC XY: 3AN XY: 71700
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 37 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 22, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 69 of the FRRS1L protein (p.Leu69Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with FRRS1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 542871). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.206T>G (p.L69R) alteration is located in exon 1 (coding exon 1) of the FRRS1L gene. This alteration results from a T to G substitution at nucleotide position 206, causing the leucine (L) at amino acid position 69 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 12, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at