rs769040844
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014334.4(FRRS1L):āc.860A>Gā(p.Tyr287Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,610,302 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_014334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FRRS1L | ENST00000561981.5 | c.860A>G | p.Tyr287Cys | missense_variant | Exon 5 of 5 | 1 | NM_014334.4 | ENSP00000477141.2 | ||
FRRS1L | ENST00000644747.1 | n.*478A>G | non_coding_transcript_exon_variant | Exon 4 of 4 | ENSP00000493964.1 | |||||
FRRS1L | ENST00000644747.1 | n.*478A>G | 3_prime_UTR_variant | Exon 4 of 4 | ENSP00000493964.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250786Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135560
GnomAD4 exome AF: 0.0000165 AC: 24AN: 1458220Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 725382
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 37 Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 839992). This variant has not been reported in the literature in individuals affected with FRRS1L-related conditions. This variant is present in population databases (rs769040844, gnomAD 0.003%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 338 of the FRRS1L protein (p.Tyr338Cys). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at