rs137852210
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM2PM5PP3_StrongPP5_Very_Strong
The NM_194277.3(FRMD7):c.70G>A(p.Gly24Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000923 in 1,083,436 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G24E) has been classified as Likely pathogenic.
Frequency
Consequence
NM_194277.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMD7 | NM_194277.3 | c.70G>A | p.Gly24Arg | missense_variant | 2/12 | ENST00000298542.9 | |
FRMD7 | NM_001306193.2 | c.70G>A | p.Gly24Arg | missense_variant | 2/12 | ||
FRMD7 | XM_017029947.3 | c.22G>A | p.Gly8Arg | missense_variant | 2/12 | ||
FRMD7 | XM_017029948.3 | c.30-6565G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMD7 | ENST00000298542.9 | c.70G>A | p.Gly24Arg | missense_variant | 2/12 | 1 | NM_194277.3 | P1 | |
FRMD7 | ENST00000464296.1 | c.70G>A | p.Gly24Arg | missense_variant | 2/12 | 1 | |||
FRMD7 | ENST00000687717.1 | n.328G>A | non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome AF: 9.23e-7 AC: 1AN: 1083436Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 349544
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | For these reasons, this variant has been classified as Pathogenic. 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: 10786). This missense change has been observed in individual(s) with X-linked infantile nystagmus (PMID: 17013395, 17768376, 25678693, 30942644). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 24 of the FRMD7 protein (p.Gly24Arg). - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Oct 23, 2020 | - - |
Nystagmus 1, congenital, X-linked Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2011 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at