rs569851503
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000100.4(CSTB):c.29A>C(p.Gln10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,529,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. Q10E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000100.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSTB | NM_000100.4 | c.29A>C | p.Gln10Pro | missense_variant | 1/3 | ENST00000291568.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSTB | ENST00000291568.7 | c.29A>C | p.Gln10Pro | missense_variant | 1/3 | 1 | NM_000100.4 | P1 | |
CSTB | ENST00000640406.1 | c.29A>C | p.Gln10Pro | missense_variant | 1/2 | 2 | |||
CSTB | ENST00000675996.1 | n.90A>C | non_coding_transcript_exon_variant | 1/3 | |||||
CSTB | ENST00000639959.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152016Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000158 AC: 2AN: 126306Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 68812
GnomAD4 exome AF: 0.00000581 AC: 8AN: 1377284Hom.: 0 Cov.: 31 AF XY: 0.00000442 AC XY: 3AN XY: 679436
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 02, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 19, 2019 | - - |
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 10 of the CSTB protein (p.Gln10Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CSTB-related conditions. ClinVar contains an entry for this variant (Variation ID: 193045). 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: "Possibly 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