X-132077907-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_194277.3(FRMD7):āc.2110A>Gā(p.Thr704Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,208,235 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_194277.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FRMD7 | ENST00000298542.9 | c.2110A>G | p.Thr704Ala | missense_variant | Exon 12 of 12 | 1 | NM_194277.3 | ENSP00000298542.3 | ||
FRMD7 | ENST00000464296.1 | c.2065A>G | p.Thr689Ala | missense_variant | Exon 12 of 12 | 1 | ENSP00000417996.1 | |||
FRMD7 | ENST00000370879.5 | c.1750A>G | p.Thr584Ala | missense_variant | Exon 8 of 8 | 1 | ENSP00000359916.1 |
Frequencies
GnomAD3 genomes AF: 0.00000889 AC: 1AN: 112437Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34589
GnomAD3 exomes AF: 0.00000547 AC: 1AN: 182832Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67530
GnomAD4 exome AF: 0.00000183 AC: 2AN: 1095798Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 361250
GnomAD4 genome AF: 0.00000889 AC: 1AN: 112437Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34589
ClinVar
Submissions by phenotype
not provided 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FRMD7-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 704 of the FRMD7 protein (p.Thr704Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at