rs755233365
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP3BS2
The NM_001540.5(HSPB1):āc.369G>Cā(p.Lys123Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000371 in 1,456,990 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K123T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001540.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPB1 | NM_001540.5 | c.369G>C | p.Lys123Asn | missense_variant | 2/3 | ENST00000248553.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPB1 | ENST00000248553.7 | c.369G>C | p.Lys123Asn | missense_variant | 2/3 | 1 | NM_001540.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248876Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135340
GnomAD4 exome AF: 0.0000371 AC: 54AN: 1456990Hom.: 0 Cov.: 33 AF XY: 0.0000359 AC XY: 26AN XY: 724804
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HSPB1 protein function. ClinVar contains an entry for this variant (Variation ID: 533812). This variant has not been reported in the literature in individuals affected with HSPB1-related conditions. This variant is present in population databases (rs755233365, gnomAD 0.005%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 123 of the HSPB1 protein (p.Lys123Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at