rs387906720
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_194277.3(FRMD7):āc.691T>Gā(p.Leu231Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 112,649 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (ā ).
Frequency
Consequence
NM_194277.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMD7 | NM_194277.3 | c.691T>G | p.Leu231Val | missense_variant | 8/12 | ENST00000298542.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMD7 | ENST00000298542.9 | c.691T>G | p.Leu231Val | missense_variant | 8/12 | 1 | NM_194277.3 | P1 | |
FRMD7 | ENST00000464296.1 | c.646T>G | p.Leu216Val | missense_variant | 8/12 | 1 | |||
FRMD7 | ENST00000370879.5 | c.331T>G | p.Leu111Val | missense_variant | 4/8 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000888 AC: 1AN: 112649Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34785
GnomAD4 exome Cov.: 25
GnomAD4 genome ? AF: 0.00000888 AC: 1AN: 112649Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34785
ClinVar
Submissions by phenotype
Nystagmus 1, congenital, X-linked Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2011 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 231 of the FRMD7 protein (p.Leu231Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with idiopathic infantile nystagmus (PMID: 17013395, 21303855). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 29976). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at