rs1557177627
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_001110556.2(FLNA):c.3861G>T(p.Gln1287His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,209,517 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001110556.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.3861G>T | p.Gln1287His | missense_variant | 23/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.3861G>T | p.Gln1287His | missense_variant | 23/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.3861G>T | p.Gln1287His | missense_variant | 23/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000889 AC: 1AN: 112484Hom.: 0 Cov.: 25 AF XY: 0.0000289 AC XY: 1AN XY: 34636
GnomAD4 exome AF: 0.00000638 AC: 7AN: 1097033Hom.: 0 Cov.: 33 AF XY: 0.00000551 AC XY: 2AN XY: 363015
GnomAD4 genome ? AF: 0.00000889 AC: 1AN: 112484Hom.: 0 Cov.: 25 AF XY: 0.0000289 AC XY: 1AN XY: 34636
ClinVar
Submissions by phenotype
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 23, 2021 | 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FLNA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 1287 of the FLNA protein (p.Gln1287His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at