9-121299872-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000373818.8(GSN):c.11A>G(p.His4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000848 in 1,179,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H4P) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000373818.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSN | NM_198252.3 | c.-9-2091A>G | intron_variant | ENST00000432226.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSN | ENST00000432226.7 | c.-9-2091A>G | intron_variant | 5 | NM_198252.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 8.48e-7 AC: 1AN: 1179468Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 574464
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2022 | The p.H4R variant (also known as c.11A>G), located in coding exon 1 of the GSN gene, results from an A to G substitution at nucleotide position 11. The histidine at codon 4 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2022 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with GSN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 4 of the GSN protein (p.His4Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.