6-144186638-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003764.4(STX11):c.11G>A(p.Arg4Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R4L) has been classified as Uncertain significance.
Frequency
Consequence
NM_003764.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STX11 | NM_003764.4 | c.11G>A | p.Arg4Gln | missense_variant | 2/2 | ENST00000367568.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STX11 | ENST00000367568.5 | c.11G>A | p.Arg4Gln | missense_variant | 2/2 | 1 | NM_003764.4 | P1 | |
STX11 | ENST00000698355.1 | c.11G>A | p.Arg4Gln | missense_variant | 3/3 | P1 | |||
STX11 | ENST00000698356.1 | c.11G>A | p.Arg4Gln | missense_variant | 4/4 | P1 | |||
STX11 | ENST00000698357.1 | c.11G>A | p.Arg4Gln | missense_variant | 2/2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251218Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135898
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461792Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727208
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74340
ClinVar
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces arginine with glutamine at codon 4 of the STX11 protein (p.Arg4Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs375610231, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with STX11-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at