NM_014334.4:c.830G>A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014334.4(FRRS1L):c.830G>A(p.Cys277Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,612,908 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
Consequence
NM_014334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FRRS1L | ENST00000561981.5 | c.830G>A | p.Cys277Tyr | missense_variant | Exon 5 of 5 | 1 | NM_014334.4 | ENSP00000477141.2 | ||
FRRS1L | ENST00000644747.1 | n.*448G>A | non_coding_transcript_exon_variant | Exon 4 of 4 | ENSP00000493964.1 | |||||
FRRS1L | ENST00000644747.1 | n.*448G>A | 3_prime_UTR_variant | Exon 4 of 4 | ENSP00000493964.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151986Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251244Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135786
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1460922Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 726774
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151986Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74228
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.983G>A (p.C328Y) alteration is located in exon 5 (coding exon 5) of the FRRS1L gene. This alteration results from a G to A substitution at nucleotide position 983, causing the cysteine (C) at amino acid position 328 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Developmental and epileptic encephalopathy, 37 Uncertain:1
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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FRRS1L-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 328 of the FRRS1L protein (p.Cys328Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at